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NMP > PharmacoKinetics > Flashcards

PharmacoKinetics Flashcards

1
Q

Pharmacokinetics NMEONIC

A

ADME

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2
Q

ADME “A”

A

Absorption, uptake of the drugs into the blood stream.

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3
Q

ADME “B”

A

Distribution,
movement of drugs from blood stream into extravascular fluids and tissues

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4
Q

ADME “M”

A

Metabolism,
Biotransformation of drugs (chemical change of the drugs)

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5
Q

ADME “E”

A

Excretion,
removal of drugs by kidneys (Plus other organs - kidneys are the main site)

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6
Q

Primary organ responsibility for metabolism of drugs

A

liver mainly. some metabolism in the gut.

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7
Q

Excretion of the drug primary organ & alternative routes

A

Kidney main , sweating, bile, faeces, breastmilk

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8
Q

“physico/physical” chemical properties of the drug are

A

Lipid soluble
water soluble

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9
Q

Lipid soluble medications excretion method

A

needs to undergo metabolism prior to excretion

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10
Q

water soluble medication excretion method

A

doesn’t need to undergo metabolism, can go straight to the kidneys for excretion

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11
Q

absorption is dependent on the route. capsules are absorbed

A

in the GI tract/ gut wall

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12
Q

capsules pass through what before getting to the blood stream

A

hepatic/portal circulation to the liver

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13
Q

liver metabolises what

A

lipid drugs

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14
Q

what does the liver do when it metabolises

A

it turns lipid soluble drugs into water soluble drugs

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15
Q

once the drug is in the systemic circulation it gets distributed to

A

the body tissues

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16
Q

after being in the circulation the drug can do two different things

A

be excreted or re-cycled through the blood stream

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17
Q

absorption definition

A

‘process of transfer of the drug from the site of administration into systemic circulation

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18
Q

bioavailability definition

A

the proportion of a drug or other substance which enters the systemic circulation (it is highest 100% for IV administered drugs)

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19
Q

what affects absorption ?

A

route, age, diet, other medicines, medical conditions, particle size and formulation, gut content, gastrointestinal motility, splanchnic blood flow

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20
Q

what factors can affect drug distribution

A

blood flow rate, drug reservoirs, permeability of capillaries for drug molecules, increased total body water as a % of total body weight (babies high water, elderly low water)

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21
Q

Why are lipid soluble drugs highly distributed

A

the cell membrane contains a fatty acid layer which allows lipid soluble drugs to easily pass through the membrane

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22
Q

water soluble drugs tend to stay where

A

in the plasma

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23
Q

Metabolism definition

A

chemically inactivates a drug by converting it into a more water soluble compound, or metabolite which can be excreted from the body

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24
Q

Cytochrome p450 system does what

A

Umbrella term for a family of enzymes which are responsible largely for drug metabolism, most common cyp3a4

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25
Q

factors affecting drug metabolism

A

alteration of liver enzyme function, hepatic blood flow, physiological status, genetic factors, other drugs

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26
Q

why would the hepatic blood flow affect drug metabolism

A

liver disease (as the blood flow through the liver is reduced)

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27
Q

why would the physiological status affect drug metabolism?

A

liver disease (what happens as we age - unhealthy lifestyle), very young or very old

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28
Q

what genetic factors can affect drug metabolism?

A

acetylation status, ultra rapid codeine metabolisers

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29
Q

what other drugs can affect drug metabolism

A

enzyme inducers or enzyme inhibitors

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30
Q

what is the acetylation status

A
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31
Q

bioavailability is to do with what step

A

absorption

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32
Q

enzyme inducing drugs

A

enhance the production of enzymes which break down drugs - faster rate

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33
Q

drugs implicated in enzyme induction include

A

phenytoin , rifampicin, carbamzepine

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34
Q

enzyme inhibiting drugs do what

A

inhibit enzymes which break down drugs leading to a decreased rated

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35
Q

drugs implicated in enzyme inhibition include

A

erythromycin, ciprofloxacin, omeprazole, amiodarone

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36
Q

excretion options for the body

A

kidneys (urine) , liver (bile ->faeces - duodenum), breast milk, lungs, sweat, tears and saliva

37
Q

what is the major characteristic of compounds excreted in urine?

A

they are polarised and water soluble

38
Q

drugs that are lipid soluble require what before urinary excretion

A

liver metabolism to increase their water solubility

39
Q

elimination via the kidney depends on what (4)

A

blood flow to the kidney, glomerular filtration rate, active secretion of drugs into the kidney tubule, passive reabsorption back into the tubule

40
Q

aging physiological changes ?

A

decreased ratio of lean body mass, decreased levels of serum albumin (main plasma protein important in drug distribution) decreased liver and renal function

41
Q

elderly patient altered drug sensitivities ( common )

A

increased response to centrally acting drugs i.e. benzodiazepines,
increased response to warfarin
decreased alpha/beta receptor responses

42
Q

aging and metabolism in the liver issues

A

physiologic changes in the liver include a reduction in size by 25-35% and a decrease in hepatic blood flow of more than 40%.
decreased blood flow leads to a reduced presystemic drug metabolism (phase 1 metabolism reduced, phase 2 metabolism generally preserved)
decreased liver size leads to reduced hepatic drug metabolism which leads to increased half life of some drugs, especially those with high clearance ratios will not be metabolised as quickly

43
Q

ageing and excretion issues

A

at 70, renal function is at best 50%, reduced glomerular filtration rate and tubular secretion lead to an increased possibility of accumulation of all drugs and metabolites eliminated via the kidneys, increased half life of water soluble drugs

44
Q

What is the half life

A

the period of time required for the concentration or amount of drug in the body to be reduced by one half

45
Q

what is plasma clearance

A

the removal of a drug from the plasma is known as clearance

46
Q

what is the volume of distribution

A

the distribution of the drug in various body tissues is known as volume of distribution

47
Q

what is the symbol what represents the half life

A

t½

48
Q

what is a steady state

A

when plasma concentration is at the correct level to be therapeutic and they are maintained by regular dosing

49
Q

The removal of a drug from the body

A

elimination

50
Q

two drugs with high half lives

A

warfarin, digoxin

51
Q

The removal of a drug from plasma

A

clearance

52
Q

Physiological factors that reduce the absorption of a drug include

A

rapid intestinal transit time, reduced splanchic circulation (such as occurs in shock) and the presence of food in the stomach.

53
Q

first pass metabolism

A
  • that is the extent to which the drug is destroyed on its first passage through the liver. If a drug is rapidly metabolised by the liver, the amount of active drug the reaches the systemic circulation will be reduced.
54
Q

Bioavailability is defined as

A

the fraction of an administered dose that reaches the systemic circulation.

55
Q

oral route advantages

A

convenient, non sterile, good absorption

56
Q

oral route disadvantages

A

first pass destruction for most drugs, gi irritation, potential for interactions, inactivation by acids, variable absorption

57
Q

sublingual advantages/disadvantages

A

avoids first pass and gastric acids/few preparations available

58
Q

rectal advantages/disadvantages

A

avoids first pass and gastric acid/ aesthetically unacceptable

59
Q

intravenous advantages/disadvantages

A

rapid access drug with complete bioavailability, useful for irritant drugs/ inceased levels of drug to the heart, sterility, risk of sepsis and embolism

60
Q

intramuscular & subcut advantages/disadvantages

A

rapid absorption, depot for slow release/painful, risk of tissue damage, absorption variable

61
Q

lungs administration advantages/disadvantages

A

large surface area, ideal for topical use/requires sound patient technique, can require bulky equipment

62
Q

What does plasma consist of?

A

Most of it is water – about 92%, whilst plasma proteins form about 7%. The remaining 1% is other dissolved solutes such as inorganic ions.

63
Q

Most, but not all, plasma proteins are manufactured in the liver including xxx

A

Albumins

64
Q

The most abundant plasma protein ?

A

albumin

65
Q

35% of plasma proteins are ?

A

globulins (contain antibodies, others transport)

66
Q

the remaining 4% of plasma proteins include things such as

A

fibrinogen, 1% metabolic enzymes

67
Q

highly bound drugs elimination may be

A

delayed

68
Q

Extensive plasma protein binding will —– the amount of drug that has to be absorbed before effective therapeutic levels of unbound drug are reached

A

increase

69
Q

why would someone with low albumin levels require less drug

A

as the drug is not bound to albumin it takes less to reach the therapeutic effect

70
Q

most common biochemical process that occurs in metabolism

A

oxidation

71
Q

what is oxidation catalysed by

A

ctyochrome p450 enzymes

72
Q

the drug is said to be xx after phase 1 reactions

A

oxidised

73
Q

phase 2 metabolism involves what

A

catabolism

74
Q

Phase 2 metabolism involves conjugation which involves what

A

that is, the attachment of an ionised group to the drug.

75
Q

what is a pro drug

A

it is a drug administered which is classed as inactive until it has completed stage 1 metabolism

76
Q

Some drug metabolites can be toxic such as those produced from paracetamol. These are usually detoxified by phase 2 conjugation joining with what?

A

glutathione.

77
Q

the process of the liver metabolising the drug is called what

A

hepatic biotransformation

78
Q

Grapefruit juice and the herb St John’s Wort inhibit what activity

A

Cytochrome P450 activity.

79
Q

Other routes of excretion from the body can include

A

bile, saliva, sweat, tears, faeces, milk and exhaled air.

80
Q

Most drugs are metabolised first prior to being excreted. However, some drugs, such as

A

aminoglycoside antibiotics are polar compounds and are excreted by the kidneys without being metabolised first.

81
Q

The excretion of drugs by the kidney utilises three processes, all which occur in the nephron, the microscopic functional unit of the kidney. These processes are:

A

Glomerular filtration,
Tubular secretion and
Tubule reabsorption.

82
Q

What influence does urine pH have on drug excretion?

A

Urine pH greatly influences whether a drug is excreted quickly or slowly.

83
Q

How can urine pH be manipulated in clinical situations?

A

It can be manipulated to control the excretion of certain drugs from the body.

84
Q

What happens to acidic drugs in alkaline urine?

A

Acidic drugs are more readily ionised in alkaline urine.

85
Q

What happens to alkaline drugs in acidic urine?

A

Alkaline drugs are more readily ionised in acidic urine.

86
Q

Why is the ionisation of drugs in urine important for excretion?

A

Ionised (polar) substances are more soluble in water, so they dissolve in body fluids more readily for excretion.

87
Q

How can aspirin poisoning be treated in terms of urine pH?

A

By making the urine more alkaline with sodium bicarbonate to increase the ionisation and excretion of salicylic acid (aspirin metabolite).

88
Q

Drug metabolism in the liver consists of?

A

pHASE 1 AND 2

NMP (3 decks)

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