L9-10 Pharmacokinetics Flashcards Preview

BMS242 Core Phys Pharm > L9-10 Pharmacokinetics > Flashcards

Flashcards in L9-10 Pharmacokinetics Deck (107)
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1

Drug effects depend on

Mechanism of action
Physiochemical properties of drugs
Concentration

2

What are the physiochemical properties of drugs

Affinity
Efficacy
Potency

3

What are the four elements which affect drug concentration

Absorption
Distribution
Metabolism
Excretion

4

Bulk flow of drug uses what

The CV system

5

4 methods of drug movement across cell membranes

Simple diffusion
Diffusion through aqauporins
Carrier
Pinocytosis

6

What are the physiochemical properties of the drugs

Lipid solubility
Diffusivity

7

What constant can be used to quantify lipid solubility

Partition coefficient

8

What constant can be used to quantify diffusivity

Diffusion coefficient

9

What type of molecules dissolve freely in lipids and penetrate cell membranes freely

Lipid soluble

10

What would the effect of using a lipid soluble molecule on rate of absoption from gut be

Increase

11

What would the effect of using a lipid soluble molecule on penetration of the brain and other tissues

Increase

12

What would the effect of using a lipid soluble molecule on renal elimination

Increase

13

What is is one of the most important determinants for pharmacokinetic characteristics of the drug

Lipid solubility

14

Describe intravenous administration
When might it be used

Injection straight into the plasma
In emergencies

15

What drugs may need to be administered intra muscularly

Drugs that would be at high risk of being metabolised in the gut

16

What types of drugs may be at high risk of being destroyed in the gut

Peptides

17

Give an example of a peptide drug

Insulin

18

What does intrathecal inject into

Direct into the CSF

19

Give an example of when intrathecal admin. may be used

During labour to administer local anasthetics

20

Define bioavailability

How much of the injected drug will make it into the plasma

21

What must be overcome in the stomach

Low pH

22

What is the portal system, what is the danger if drugs enter

Involving the liver
Drugs would be metabolised by the liver

23

What can be controlled with a drug in tablet form

The rate at which the active form of the drug is liberated from the tablet

24

When may the oral route be unsuitable

When vomitting
GI problems - ulceration
Young children may find it hard to swallow

25

If the drug target was the GI tract what would be the favoured method of administration

Rectal route

26

What is usually the difference between cheaper and more expensive over the counter drugs

Particle size - tends to be larger with cheaper drugs

27

What is percutaneous administration

Absoprtion through the skin

28

Example of a drug that is adminstered percutaneously

Nicotine via patches

29

What is the problem with percutaneous administration

Skin is highly impermeable
Drug would need to have a high lipid solubility

30

What would the targets of drugs be that were adminsistered percutaneously

Nuclear receptors

31

example of a type of drug that would be administered percuansouslt

Hormone

32

What two classes of drug are administered by inhalation

General anasthetics and drugs which target the lungs

33

What sort of molecules would cross the placenta

lipophilic (soluble in lipids)

34

Most drugs are weak X and X

Acids and bases

35

Difference between a weak and strong acid

Strong - fully dissociate
Weak - partially dissociate

36

Describe the dissociation for a weak acid

HA <==> A- + H+

37

What does pKa represent

The pH at which 50% of the acid is in its disociated form

38

State the Henderson-Hasslebach equation

pKa = pH + log (HA/A-)

39

What can be said about weak acids at a low pH

They will be undissociated

40

What can be said about weak acids at a high pH

They will be dissociated

41

pKa of aspirin

3.5

42

Aspirin has a pKa of 3.5, state what will happen in the following

Gastric juices at pH 3

Plasma at pH 7.4

Urine at pH 8

gastric juices, pH low therefore undisociated and able to move freely across the membranes

Plasma pH is higher therfore more will dissociated

In urine pH much higher therfore lots dissociated and it is trapped

43

How can the weak acids become trapped

Undissoicated HA form is non polar so can diffuses across the membrane
Once dissociated both A- and H= have charge, so these are not able to cross the membrane

44

What can be used to treat aspirin poisoning

Increasing the plasma pH by adding HCO3-, weakly acidic drugs are drawn out of the CNS into the plasma where they become trapped

45

Two types of carrier mediated transport

Solute carrier (SLC) transport
ATP binding cassettes (ABC) transporters

46

SLC transport is

Passive

47

ABC transport is

Active

48

Two consideration to consider for rate at which drug is able to be transported across the cell membrane

Number of channels in the membrane
MAX rate that these channels are able to function at

49

What two considerations must be made for normal physioligcal fucntion if a large ammount of drug has to be transported across a membrane

Build up on one side if rate is slow
Impact on transport of the endogenous drugs

50

What is OCT1

Organic cation transporter 1

51

What is metformine

Drug used to treat type 2 diabetes

52

What do genetic variants of OCT1 show when treated with metformin

Different response effects due to single nucleotide polymorphisms (SNPs)

53

4 major body compartments

ECF
ICF
Transcellular
Fat

54

3 compartments of the ECF

Plasma
Interstitial fluid
Lymph

55

Conc of plasma to b.w.

4.5%

56

Two things that determine the distribution of a drug

Permeability and lipid solubility

57

What compartment are non polar drugs able to enter easily

Fat compartment

58

Why does drug entering fat cause problems for people with varying body masses

Ammount of drug entering the fat compartment can vary so concentration of drug in the plasma will vary also

59

What protects the fetus

Placenta

60

What prevents the CNS from drugs

bbb

61

What type of cell junction are involved in the formation of the blood brain barrier

Tight junctions between endothelial cells

62

What is the BBB impermeable to

Impermeable to H20 soluble molecules

63

Give an example of two substances that the BBB would be impermeable to

Peptides, antibiotics

64

What type of molecules are able to cross the BBB, give two examples

Lipid soluble molecules
Ethanol and caffine

65

What happens to the BBB during inflammation, what disease does this occur in and how may it be treated

Tight junctions become leaky
E.g. in meningitus
Can treat with IV penicillin ==> able to pass through the BBB due to the leaky tight junctions

66

Define the chemoreceptor trigger zone

An area of the medulla that recieves inputs from blood borne drugs and hormones and is able to initiate vomitting

67

What NT has receptors in the chemoreceptor tirgger zone

Dopamine

68

What extra precaution must be taken when treating Parkinsons with dopamine

Dopamine may also be an agonist in the chemoR trigger zone
Should be given with a dopamine antagonist which is also not able to cross the BBB and therefore is unable to cause vomitting

69

Albumin is what? What is it able to do?

Plasma protein
May bind to drugs

70

Drugs that are bound to albumin are not

Filtered

71

What is the binding capacity of albumin

1.2mmol

72

What is the affect of albumin binding to a drug

It would reduce the concentration of free drug in the plasma

73

What must be taken in consideration when a high concentration of drug is required for the response but plasma protein binding occurs

If binding occurs then won't be as high conc of free drug in the blood ==> response may not be seen

74

What would possibly be the implications if a person was taking more than drug which is known to bind to plasma proteins

One drug will outcompete and displace the other from binding causing the concentrations of drug in the blood to vary dramatically

75

Issues with prescribing a drug to someone with low body fat

Effects can be longer lasting as less is partitioned into the fat compartment
Drug concentration reaching target very high ==> as no reservoir to mop up the drug

76

Phase 1 reaction anabolic or catabolic

Catabolic

77

What does a phase 1 reaction produce

More reactive compounds

78

Phase II reaction anabolic or catabolic

Anabolic

79

What does a phase 2 reaction involve

Conjugation to produce more inactive compounds

80

Example of a microsomal enxxyme found in the liver

Cytochrome P450s
Alcohol dehydrogenase
MAO

81

What must happen in the liver in order for the drug to be metabolised

It must cross the plasma membrane

82

What are prodrugs

Drugs which only become active once they have been metabolised

83

What two things govern the rate of enzymatic metabolism

Ammount of enzyme
The max rate the enzymes are able to function at

84

Increasing the ammount of enzyme present is known as

Induction

85

What is the knock on effect of adding more enzyme - how would this effect a second dose

Drug is being broken down more efficiently so a dose of the same concentration would have a decreased effect

86

If the drug is able to combine with bile what is avoided

Metabolism

87

What reactions occur during the phase one reaction of aspirin

Oxidation
Hydroxylation
Dealkylation
Deamination
Hydrolysis

88

State the 3 types of products in the elimination of aspirin

Drug
Derivative
Conjugate

89

State the 3 products in the elimination of aspirin

Aspirin
Salicylic acid
Glucuronide

90

What is the type of reaction aspirin occurs during its phase II reaction

Conjugation

91

Why is paracetamol toxic when overdose taken

During phase I reaction a highly toxic product to the liver is produced

92

Over how many genes for cytochrome p450 enzymes

Over 57

93

What are the individual variations in P450 enzymes

Single nucleotide polymorphisms

94

What is the effect of different isoforms of P450 enzymes

They react with different drugs

95

IA2 is a

Inducer of P450 drug metabolism

96

3 examples of IA2

Brocoli
Brussel sprouts
Tobacco

97

Glomerular filtration will remove drugs with a

Low Mr

98

Will drugs bound to albumin be filtered

No - Mr of 68'000

99

What is active tubular secretion

Transport of drugs directly into the urine

100

How do liophilic molecules get excreted

Passive diffusion across the plasma membrane

101

Describe how penicillin is cleared

Cleared on a single pass

102

Describe how diazepan is cleared from the body

Cleared very slowly

103

What are two other methods for elimination of drugs

GI excretion - bound up by food
Expired by the lungs

104

Time course of clearance follows what

A mono exponential decay

105

Time course of clearance is determined by

Metabolism and excretion

106

Is half life always constant for the same drug

Yes

107

What is half life

Time taken for the concentration of drug to fall by half