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303 MEDIMAGE > 2. ADME I: absorption and distribution of drugs > Flashcards

2. ADME I: absorption and distribution of drugs Flashcards

1
Q

what does the phrase “route of drug administration” mean

A

the pathway that a drug enters the body

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2
Q

how does the route of drug administration affect the amount of drug

A

amount of drug that reaches the target tissue can be altered if proper route is not used

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3
Q

what 2 factors is affected by the route of administration for a drug

A

rate and extent of drug absorption

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4
Q

what are the 3 main routes of drug administration and what do they mean

A

enteral (GI tract)
Parenteral (routes other than GI tract)
topical

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5
Q

what are the 2 methods of enteral drug administration

A

oral (po)

rectal

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6
Q

what are the 6 methods of parenteral drug administration

A 
intervenous
intramuscular
subcutaneous
transdermal
respiratory tract
sublinggual/buccal
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7
Q

what is enteral drug administration

A

absorption of drug by GI tract

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8
Q

what does parental IV distribution of drugs allow and what is it useful for

what is done to prevent adverse effects

A

precise conc in blood and useful for immediate effect

injected over a min/2 to prevent very high conc in injected vein which may lead to adverse effects

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9
Q

why is Intramuscular distribution of drugs unpredictable and erratic

A

difference in vascularity means that rates of absorption differ based on location and may be slow

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10
Q

what is the drug absorption rate of subcutaneous drug distribution and why

A

injection under skin drug absorption is slower than intramuscular due to poor vascularity

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11
Q

what is transdermal drug distribution

A

across skin released into systemic circulation

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12
Q

what is the drug absorption rate of respiratory drug distribution and why

A

absorbed in large alveolar area which has good blood supply so rapid absorption

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13
Q

what is sublingual and buccal drug distribution

A 
sublingual = under tongue
buccal = in cheek pouch
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14
Q

what is sublingual and buccal drug distribution useful for

A

useful for drugs that are metabolized in gut as vessels in mouth bypass the gut and liver and go straight to systemic circulation

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15
Q

what do topical drug distribution avoid and where does it work

A

avoids systemic effects

only works where it is applied

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16
Q

is transdermal drug distribution the same as topical? why/why not

A

topical is intended for effect at drug application location but transdermal is absorbed through skin to reach systemic circulation to get to where they are needed

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17
Q

what are the 2 main paths of drug administration

A

systemic vs local/topical administration

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18
Q

drugs that need to be distributed throughout the body requires what step

A

requires entry into systemic circulation

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19
Q

what is the first step in the passage of a drug

when is this not the first step

A

absorption is the first step unless the drug is directly introduced into the blood stream (eg IV)

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20
Q

what is drug absorption

and what does it require in terms of its passage

A

transfer of drug from administration site to the systemic circulation

requires passage through biological membranes

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21
Q

why is absorption of the drugs delayed and incomplete for orally administered drugs

A

several barriers to overcome and it needs to be absorbed

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22
Q

what is the absorption rate

A

how rapidly the drug gets from site of administration to the systemic circulation

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23
Q

what is the absorption extent

A

how much of the administered dose enters the systemic circulation

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24
Q

what is the order of rate of absorptions for the following distribution routes

IV, Oral, Subcutaneous, Inhalation, intramuscular, rectal, sublingual

explain why youve placed them in that order

A

IV (shortest/fastest), inhalation, intramuscular, subcutaneous, rectal/sublingual, oral, transdermal (longest/slowest)

IV fastest as no absorption needed
transdermal slowest as needs to penetrate thick skin to reach circulation

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25
Q

why is topical drug distribution not included in the ordering of absorption rates

A

only act locally and have minimal penetration in skin layer so low absorption

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26
Q

what is the bioavailability and what does it mean when its =1 and <1

A

fraction of dose absorbed

=1 means 100% enters circulation
<1 means less than all the dose is absorbed/incomplete absorption

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27
Q

is bioavail related to the rate or extent of drug absorption

A

extent

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28
Q

For a orally distributed drug, why would the final dose in systemic circulation be less than the amount we started with

A

Orally, drug has to travel through biological membranes and organs before reaching systemic circulation so portions of dose can be lost on the way

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29
Q

where are the 2 locations where the drug may reduce in dose when taken orally and why

A

GI tract, intestines, Liver

Oral must cross gut epithelium in wall to enter portal circulation. Gut epithelium cells have efflux transporters, so drug may be returned to gut and excreted from GI tract

Some drugs may be metabolized in intestinal wall

Liver can do extensive metabolism as liver is rich in metabolism enzymes, this is known as the first pass hepatic metabolism

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30
Q

what is the first pass hepatic metabolism effect and what does it do to the drug dose

A

Liver can do extensive metabolism as liver is rich in metabolism enzymes, this process of metabolizing drugs is known as the first pass hepatic metabolism

First pass effect can reduce drug dose to significant amounts and reduce bioavail

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31
Q

what are the 2 most popular routes of drug administration

A

intravenous and oral

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32
Q

what is the rate and extent of absorption for intravenous drug administration

A

immediate rate and extent is 100%

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33
Q

what is the rate and extent of absorption for oral drug administration

A

gradual rate and incomplete extent

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34
Q

what are the advantages of IV administration

6 advantages

A

rapid

precise control (100% bioavail)

can be administered as bolus/infusion/both

avoids absorption problems or drug breakdown before entering blood

good for orally irritating drugs

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35
Q

what are the disadvantages of IV administration

3 disadvantages

A

requires hospitalization

careful preparation of injected material (sterile, nonparticulate)

most hazardous (as no recall and exposed to high conc in short time frame so could lead to toxicity)

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36
Q

what are the advantages of oral administration

3 advantages

A

safest

most convenient (anyone can administer it)

economic

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37
Q

what are the disadvantages of oral administration

2 disadvantages

A

slow (1/2 - 3hrs for effect)

unpredictable (with regard to rate, extent, reproducibility)

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38
Q

what is absorption like in the oral mucosa and why

A

limited absorption

thin epithelium and highly vascularized but limited absorption due to short contact time

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39
Q

what is absorption like in the oesophagus and why

A

no absorption

due to rapid transmit time (doesn’t lie in contact with drug for sufficient time)

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40
Q

what is absorption like in the stomach and why

A

low

acidic pH and small surface area and lined by thick mucosa layer

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41
Q

what is the stomach a site of absorption for in terms of drug properties and why do these properties allow passage

A

weak acids and neutral drugs

acidic pH

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42
Q

what is the main absorption site of drugs in the body

A

small intestine

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43
Q

what does the small intestine have that affects the absorption rate of drugs

A

villi increases the surface area and is highly vascularized

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44
Q

what is the absorption extent of the large intestine like compared to the small intestine

A

little absorption occurs in the large intestine compared to the small intestine

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45
Q

what in the large intestine can affect the metabolism of drugs

A

colon microbiota and metabolizing enzymes can break down drugs

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46
Q

what are drug characteristic factors affecting GI absorption of oral drugs

6 factors

A 
water/lipid solubility
ionisation
chem stability
liability for metabolism
dosage form
dissoluton rate
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47
Q

what is a drugs chemical stability

A

drug needs to survive before its absorbed from intestinal fluid

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48
Q

what is an example of chemical stability affecting GI absorption of oral drugs

A

some drugs prone to metabolism such as hydrolysis of esters

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49
Q

what are 2 solid dosage forms of oral drugs

A

tablet and capsules

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50
Q

what are the 4 types of tablet drugs

A

compressed
film coated
enteric coated
controlled release

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51
Q

what are the 2 types of capsule drugs

A

powder

liquid

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52
Q

what are 2 examples of solid dosage forms that have local effects

A

lozenges and suppositories

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53
Q

describe the coating if present of compressed tablet drugs

A

no special coating

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54
Q

describe the function of the coating - if present - of enteric coated tablet drugs and what this means for the tablet

A

carry medications that can be chemically destroyed by stomach so cant be crushed or chewed

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55
Q

describe the function of controlled release tablet drugs and effect this has on compliance

A

gradually releases drugs over several hours and there can be multiple coatings depending on thickness of coating

release particles over varying periods so can reduce dosage frequency and increase patient compliance

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56
Q

what are 3 liquid dosage forms

A

solutions
emulsions
suspensions

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57
Q

what are 2 topical dosage froms

A

semisolids

transdermal patch

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58
Q

what is a type of parenteral dosage form

A

ampoules

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59
Q

what are solutions type liquid dosage forms

A

usually water

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60
Q

what are emulsions type liquid dosage forms

A

fine droplets of oil and water

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61
Q

what are suspension type liquid dosage forms

A

medication suspended in water

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62
Q

what are parenteral dosage forms commonly

A

injections

63
Q

how do transdermal patches work how are they different from semisolids

A

topical semisolids = creams and gels not designed to be absorbed in circulation

transdermal = designed to be absorbed into circulation

64
Q

what is biopharmaceutics

A

studies methods for achieving effective drug administration

use drugs physio-chem properties to design dosage forms

65
Q

the dosage form directly influences what 2 things

A

influences drug release and rate of drug made avail for drug absorption

66
Q

drugs in solid form must do what and undergo what before they can be absorbed

A

disintegrate - break into smaller particles

undergo dissolution - dissolve in body fluids

67
Q

in general absorption of in liquid form has what speed compared to drugs in solid form and why

A

liquid is faster than solid

solid form needs more time to enter body than drug in liquid form

68
Q

order the following forms of drugs in rate of absorption from fastest to slowest

capsules, suspensions, tablets, solutions, enteric-coated tablets, coated tablets

A

solutions > suspensions > capsules > tablets > coated tablets > enteric-coated tablets

69
Q

what are the 2 kinds of release

A

intermediate and modified

70
Q

immediate release solid oral dosage forms lead to what effect on absorption

A

disintegrate rapidly leading to rapid absorption

71
Q

when is immediate release needed? ie in what kind of drugs

A

when rapid drug levels are needed

eg in pain

72
Q

what does modified/controlled release do to absorption

A

can slow the release of drug avail for absorption

73
Q

what are drug dosage form use modified controlled release

A

enteric coated drugs are stable under acidic conditions but dissolve in high pH solns in small intestines

74
Q

what is the process required for solid dosage form to turn into granules

A

disintergration

75
Q

what is the process required for granules to fine particles

A

disaggregation

76
Q

what is the process required for solid dosage form to drug avail for absorption

A

dissolution (minor)

77
Q

what is the process required for granules to drug avail for absorption

A

dissolution (major)

78
Q

what is the process required for fine particles to drug avail for absorption

A

dissolution (major)

79
Q

what is the effect of rate of absorption on concentration profile

A

how quickly drug reaches peak conc

80
Q

what are the values on the x and y axis on the conc profile graph

A

x axis = time in hours

y axis = plasma conc in mg/L

81
Q

what aspect of action does rate of absorption impact

A

onset of action

82
Q

why does drug effect have to be above the min therapeutic level

A

below the min therapeutic level it will not lead to the desired therapeutic effect

83
Q

what is the absorption phase on the concentration vs drug effect graph

A

when you see increase in drug conc

84
Q

how do you tell on the graph that A and B have same rate of absorption and B is slower than A in terms of absorption rate

A

reaches max conc around same time so have equal rate of absorption

B takes longer so slowest rate of absorp

85
Q

what is the effect of extent of absorption on concentration profile

A

total exposure to the drug in a given time period

86
Q

exposure to a drug is given by what in the drug conc vs time graph

A

given by area under plasma conc time curve

87
Q

what are the 3 patient characteristics that affects the GI absorption of oral drugs

A

gastric emptying rate

intestinal mobility

drug-food interactions in the gut

88
Q

what is the gastric emptying rate

how long is the normal gastric emptying rate

A

time taken for stomach to empty after feeding

normally 4hrs

89
Q

how does the gastric emptying rate affect drug absorption

A

its a rate limiting process for drug absorption

90
Q

gastric emptying rate is an essential consideration for what kinds of drugs

A

drugs that are broken down in stomach or that cause stomach ulcers

91
Q

accelerated gastric emptying can have what effect on the rate of drug absorption

A

accelerated emptying rate = increase rate of drug absorption as most drugs will move to next part of GI tract which is where most drugs are absorbed (small intestine)

92
Q

the gastric emptying rate is decreased by what 7 factors

A 
volume and content of meal
hot meals
vigorous exercise
emotion
pain
disease
gastric ulcer
93
Q

what kind of drug administration can influence gastric emptying

A

co-administered drugs (drugs taken together)

94
Q

how does intestinal mobility affect the absorption of drugs

explain for high motility and low motility

A

time taken for drugs to pass through GI tract affects absorption

high motility can prevent adequate absorption as reduces time in contact for absorption to take place

Low motility drug moves too slowly along gi tract so metabolism can increase and can reduce absorption of drugs due to enzymes etc

95
Q

what is a pathological aspect involving gut that can affect adequate absorption

A

disease state influences intestinal mobility

eg diarrhoea, gastroenteritis, irritable bowel syndrome,

96
Q

what do drug food interactions in the gut do to drug absorption

A

drugs may interact with food in GI tract affecting rate and extent of drug absorption

97
Q

what does grapefruit juice do to drugs

A

affects metabolism of co-administered drugs

98
Q

what do dairy products do to drugs and how does this affect absorption

A

drugs interact with dairy products to dorm insoluble complex with metal ions

reduces absorption

99
Q

what is drug distribution and why is it needed

A

transfer of drug from blood circulation to various tissues in the body

essential for drug to get to its site of action

100
Q

can different tissues/organs receive diff levels of drug and can it remain in diff tissues/organs for diff amounts of time

A

yes to both

101
Q

distribution factors can be affected by what 2 factors

A

access of drug to its site of action

relative distribution of a drug betw blood and rest of body

102
Q

what are 2 factors affecting access of a drug to site of action

A

Poor perfusion = area like tumors have limited blood supply so limited drug distribution

Physical barriers

103
Q

what is the main system to is responsible for drug distribution in the body

A

circulatory system

104
Q

what do arteries and veins do

describe the route of blood flow in circulatory circuit

A

arteries carry blood to tissues and veins return blood back to heart

Systemic circ -> right heart -> pulm circulation -> left heart -> rest of body

105
Q

what is the path that IV drugs travel before being pumped to rest of body

A

to right heart -> pulmonary circulation -> left heart -> rest of body

106
Q

describe capillary permeability and how does this affect drugs travelling in the bloodstream

A

most capillaries are relatively porous

drugs leave blood regardless of whether they are poorly lipid soluble, charged or polar

107
Q

what are exceptions for capillary permeability in terms of when drugs cannot leave blood and explain why

A

brain capillaries have no pores and an additional layer of glial cells

AKA = Blood brain barrier

108
Q

what is the blood brain barrier and what does it do to the passage of drugs

A

highly selective permeability barrier

effective barrier against passage of many drugs

109
Q

what are 3 components of the BBB that affect drug permeability

A

endothelial cells form tight junctions = CNS entry restricted as blood capillary endothelial cells are tightly joined and have few/no pores

high expression of efflux transporters = transport some chem back into blood

capillaries surrounding astrocytes further restrict access

110
Q

in the BBB transcellular passive diffusion is restricted to what kinds of drugs

A

small, unbound lipophilic drugs

111
Q

tight junctions and lipid membrane of cells limit access of what kind of drugs and why

A

Tight junctions and lipid membranes of cells limit access of water soluble drugs

also lipid soluble drugs restricted as there are so many lipid membranes to cross

112
Q

the BBB is less permeable to more ____ drugs than other areas of the body

A

hydrophilic

113
Q

why does the BBB only restrict access to many substances and why is it not just an absolute barrier

A

some drugs undergo active transport

114
Q

what are the 2 types of fluid in the cells fluid compartments

A

extracellular fluid

intracellular fluid

115
Q

what is intracellualr fluid

A

all fluid enclosed in cells by plasma membrane (fluid in cells)

116
Q

what is extracellualr fluid

A

fluid that surrounds cells (outside of cells)

117
Q

what 2 components make up the ECF

A

interstitial fluid and plasma of blood

118
Q

is the boundary between the ECF and ICF porous

A

no

they are harder to cross

119
Q

in an average 70kg person how many L of plasma do they have

A

3L

120
Q

in an average 70kg person how many L of Interstitial fluid do they have

A

11L

121
Q

in an average 70kg person how many L of ICF do they have

A

28L

122
Q

temporarily disregarding active transport, how many L of fluid does water soluble and low molecular weight drugs occupy and why

A

14L

Lower molecular weight drugs or water soluble drugs will occupy volume of plasma as well as interstitial fluid but as they are polar, they cant cross the plasma membrane. These drugs can occupy close to 14L (plasma + interstitial fluid)

123
Q

temporarily disregarding active transport, how many L of fluid does lipid soluble drugs occupy and why

A

42L

Lipid soluble drugs are able to diffuse across cell memb to reach ICF so volume these drugs can occupy is close to 42L (volume of total water)

124
Q

temporarily disregarding active transport, how many L of fluid does high molecular weight drugs occupy and why

A

3L

they are confined to plasma as they are too big to move out of the capillaries

125
Q

what is the relationship between drug distribution and blood flow

A

tissue that receives blood receives more drugs

126
Q

which 3 organs receive drugs very rapidly and why

A

kidneys, liver and heart

well perfused with blood

127
Q

which 3 tissues receive drugs very rapidly and why

A

muscle, fat and skin

less perfused with blood

128
Q

what is plasma protein binding

A

drugs frequently bind to proteins in plasma

129
Q

what does plasma protein binding do to drug distribution

explain why it has that effect

A

opposing effects on distribution

bound drug will remain in circulation as they cant penetrate cell memb and therefore will be pharmacologically inactive and is protected from metabolism and elimination

130
Q

is protein binding reversible

A

usually yes

131
Q

what are the 6 routes of contrast administration

explain them in layman’s terms for where they are delivered via

A

intra:

  • arterial = artery
  • thecal = CSF
  • articular = joint
  • synovial = synovial cavity of joint
  • cavitary = body cavity (eg uterus, cervix etc)
  • peritoneal = peritoneal cavity
132
Q

what is the most common route for contrast media delivery

where is CM introduced in this delivery option and what is avoided

A

intravascular = CM introduced to systemic system so bypasses absorption process completely

133
Q

which way do veins and arteries move blood

A 
veins = towards heart
artery = away from heart
134
Q

what happens to drugs delivered intravenously - what is its path

A

drug carried through heart and diluted in blood before reaching tissues/organs

135
Q

what happens to drugs delivered intraarterially - what is its path

A

drug carried directly into tissues

136
Q

what is one benefit and one downside to using intra-arterial injection for contrast media

A

similar contrast enhancement can be achieved with less contrast medium

but is more invasive and less safe

137
Q

the rate and extent of distribution of contrast media will influence what 2 factors of contrast enhancement

A

intensity and timing of enhancement

138
Q

the distribution of contrast media is dependent on what

A

blood flow

139
Q

how is contrast media distribution related to tissue perfusion

A

highly perfused tissues and organs show high contrast enhancement during initial circulation

140
Q

what happens to the contrast media as it circulates the body and where in the body is this most important

A

diluted

more diluted in organs distal from injection site regardless of tissue perfusion

141
Q

how does injection rate affect contrast in vessels

what is the pro and con of faster injection rate

A

higher rate = higher contrast

Faster injection can increase peripheral venous blood flow which increase rate of distribution allowing contrast delivered quickest to central compartment, but incr blood flow means that contrast doesn’t remain for long time so shortens scan opportunity

142
Q

why must contrast injection be done at equal rate or greater rate to blood flow

A

if its too slow, cardiovascular system will signif dilute conc of contrast agent before imaging takes place and rapid injection limits early dilution effect of cardiovascular system

143
Q

what are the 2 injection factors to consider for contrast media

A

speed and duration of injection

injection site in relation to site examined

144
Q

how does injection site in relation to site examined impact contrast media

in terms of central and peripheral veins pros/cons

A

central venous injections shorter travel distance so quicker peak enhancement but located deeper

peripheral veins smaller and superficial so easier to reach but further away

145
Q

what is the saline push effect for contrast media

why is this useful x 3 things

A

immediately after contrast media administration flush with saline - this flushes any remaining contrast media from catheter

thereby it:

  • increases the amount of contrast agent avail for distribution
  • pushes contrast media bolus further into blood circulation
  • decreases contrast media amount in locations where its not needed
146
Q

what are the 4 patient factors

2 main and 2 less important ones

A

cardio output and body size important

age/sex and hepatic disease less important

147
Q

how does body size of patient affect contrast enhancement

explain how

A

affects its intensity

larger blood volumes in larger patients so greater dilution and reduced conc of contrast in blood = results in lower contrast enhancement

148
Q

how does cardiac output of patient affect contrast enhancement

explain how

A

affects timing of contrast enhancement

decreased CO means contrast arrives more slowly and clears more slowly leading to prolonged enhancement

149
Q

what is the equation for Cardiac output

what is CO and what are the units involved in the equation

A

CO = HR x SV

amount of blood flowing into circulation per min

SV = ml/beat
HR = beat/min
150
Q

what 5 factors affect cardiac output and how

A

Exercise = increases both HR and SV

Age = decrease O2 consump and muscles so lower CO

Body size = larger size has larger CO

disease and metabolism = increase metabolism in tissues and O2 use and also releases vasodilator products leading to decrease vessel resistance = increases CO

151
Q

how does age and sex of patient affect contrast enhancement

explain how

A

diff betw men and women due to diff in body size and blood volume (M>F)

CO reduces with age so enhancement may be stronger in elderly patients than younger

152
Q

how does hepatic disease of patient affect contrast enhancement

explain how

A

may later perfusion and thus enhancement profile

153
Q

what happens to contrast and the BBB normally vs when there is damage to BBB

can there be adverse reactions if contrast gets into the brain

A

dont normally cross BBB freely to enter the CNS

contrast media can enter brain when disease alters BBB’s permeability and can produce toxic effects on neurons and astrocytes when they penetrate altered BBB (neurotoxicity)

303 MEDIMAGE (14 decks)

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