ADME Flashcards
1
Q
what does ADME stand for
A
-Absorption
- Distribution
- Metabolism
- Excretion
2
Q
what does ADME describe
A
the key kinetic principles
3
Q
what is absorption
A
how a drug moves from its site of administration into the bloodstream
4
Q
what is distribution
A
movement of the drug between blood and tissues
5
Q
what is metabolism
A
conversion of drugs into more hydrophilic metabolites
6
Q
what is excretion
A
removal of drugs and/or metabolites from the body
7
Q
where are the majority of drugs absorbed
A
in the small intestine
8
Q
what conditions can slow the absorption of drugs
A
- gastroparesis in DM
- colectomies
9
Q
what features predict drug movement
A
- molecular size
- degree of ionization
- lipid solubility
- protein binding
10
Q
to pass through lipid membranes drugs must be:
A
non ionized
11
Q
to be water soluble, drugs need to be:
A
ionized
12
Q
what happens when a strong acid interacts with water
A
a complete irreversible reaction
13
Q
what happens when a weak acid interacts with water
A
a reversible reaction
14
Q
most drugs are either:
A
weak acids or weak bases
15
Q
what happens to an acidic drug in an acidic pH
A
it is non-ionized and protonated
16
Q
what happens to a acidic drug in a basic pH
A
ionized, deprotonated
17
Q
what happens to a basic drug in acidic pH
A
ionized, protonated
18
Q
what happens to a basic drug in a basic pH
A
non-ionized, deprotonated
19
Q
acids are _____ when protonated
A
non -ionized and fat soluble
20
Q
bases are _____ when deprotonated
A
non-ionized
21
Q
what is pKa
A
the pKa is the pH at which there are equal amounts of protonated and non-protonated
22
Q
when pH = pKa:
A
protonated equals non protonated
23
Q
when pH < pKa:
A
protonated form predominates
24
Q
when pH > pKa:
A
non-protonated form predominates
25
only the ______ form of the drug can readily cross the lipid membrane
non-ionized
26
ratio of ________ and ______ influences the rate of absorption
non-ionized and ionized
27
what is ion trapping
because ionized molecules cant cross the membrane, can effectively trap them and enhance excretion
28
how do acidic environments of abscesses affect ionization state of local anestehtics
- local anesthetics are basic and have a high pKa
- abscesses have a lower pH
- when a basic drug is in an acidic pH the protonated and ionized form predominates - water soluble
- the anesthetic will hang in the abscessed fluid which makes it harder to cross membrane and harder to numb
29
what anesthetic would take the longest time to work in an abscessed area
bupivicaine
30
what anesthetic would be the fastest to numb in an abscessed area
mepivacaine
31
absorption is the movement of a drug from its site of administration into the ______
central compartment
32
absorption is the process of:
dissolution and diffusion
33
what is bioavailability
fraction of drug that reaches the systemic circulation intact
34
what is the bioavailability of IV drugs
100%
35
bioavailability is affected by:
route of administration
36
what is hepatic extraction ratio
fraction of drug in blood that is irreversibly removed during one pass through the liver
37
what is first pass clearance
extent to which a drug is metabolized by the liver during its first pass in the portal blood through the liver to systemic circulation
38
drugs with low hepatic extraction will have _____ first pass clearance
low
39
first pass effect occurs due to metabolism in:
- gut bacteria
- intestinal brush border enzymes
- portal blood
- liver enzymes
40
describe low hepatic extraction
- low first pass clearance
- change in hepatic enzymes wont have significant effect on first pass clearance
41
describe high hepatic extraction
- high first pass clearance
- bioavailability is lower
- changes in enzyme function will have large effect on first pass effect
42
what is an example of a drug with high hepatic extraction
morphine
43
what is an example of a drug that undergoes enterhepatic recirculation
clindamycin
44
what are the 2 types of routes of administration
enteral and parenteral
45
what is parenteral route of transmission
any drug that bypasses the GI system to get to the blood
46
what are the advantages and disadvantages of enteral administration
-A: most common route, safest, easier, most economical
- D: limited absorption, emetogenic potention, subject to first pass, absorption may be affected by food or other drugs, irregularities in absorption or propulsion
47
what are the advantages and disadvantages of parenteral administration
-A: not subject to first pass, most rapid onset, ability to titrate, doesnt require patient cooperation
- D: greater patient discomfort, requires additional training to administer, concern for bacterial contamination, infection associated risks
48
what are the infection associated risks with parenteral administration
- extravasation
- intra-arterial injection
- limb loss
49
in oral administration absorption is governed by:
- surface area for absorption
- blood flow to site of absorption
- dosage form administered
- ionization status ( lipo vs hydrophilic)
- concentration at site of absorption
50
what orally administered drugs have enteric coating
drugs destroyed by gastric secretions, low PH, or that cause gastric irritation
51
what is the risk associated with enteric coating on orally administered drugs
risk of bezoar formation
52
orally administered drugs have ____ release
delayed
53
what are the parenteral routes of administration
- intravenous
- intramuscular
- subcutaneous
- intradermal
- inhalation
- intranasal
- intrathecal/epidural
- topical
- subgingival
54
describe intravenous injections and their bioavailability
- 100%
- immediate onset, bypasses GI absorption
- best for emergencies
55
describe intramuscular injections and their bioavailability
- 75-100%
- irritatnig drugs given this route
- not as rapid response as IV
- depot preparations (sustained release)
56
describe subcutaneous injections and their bioavailability and give examples
- 75-100%
- slower absorption than IV or IM
- little risk of intravascular injection
- ex: insulin, mechanical pumps, heparin
57
describe intradermal injections and examples
-small amounts of drug
- tuberculosis skin test, local anesthetics
58
describe inhalation route and its bioavailability
- 5-100%
- almost as rapid as IV (method of abuse)
- delivered directly to lung (good selectivity) - minimal systemic side effects
- gases, aerosols of solutions and powders - good for respiratory conditions
59
describe intranasal administrations and their bioavailability
- 5-100%
- vasopressin for tx of diabetes insipidus, calcitonin (osteoporosis)
- method of drug abuse
60
describe intrathecal/epidural injections and examples
- subarachnoid space of spinal cord into CSF
- lumbar puncture-baclofen in MS, regional anesthetic in delivery, morphine drip
61
describe topical route of administration and the bioavailability
- skin, oral mucosa, sublingual, rectal
- avoids 50% of first pass metabolism
- when local effect is desired but can provide systemic effects
- sublingual (100%), rectal (50%) bypasses liver - good bioavailability
- transdermal controlled release
62
what are examples of transdermal controlled release drugs
- scopolamine
- nitroglycerin
- nicotine
- fentanyl
63
describe subgingival route of administration
- perio specific uses: doxycycline (atridox)
- minocycline (arestin)
64
what happens in distribution
the administered drug leaves the blood stream and enters other compartments
65
what is distribution dependent on
- cardiac output
- capillary permeability
-blood flow
66
what organs get the most to least blood distribution and what is the number of each
- kidney: 360 mL/min/100gm
- liver: 95 mL/min/100gm
- heart: 70 mL/min/100gm
- brain: 55 mL/min/100gm
67
what are the 3 main compartments
- central
- peripheral
- special compartments
68
what is in the central compartment
well perfused organs and tissues such as heart, blood, liver, brain, kidney. drug equilibrates rapidly
69
what is in the peripheral compartment
- less well perfused organs/tissues such as adipose, skeletal, muscle
70
what is in the special compartments
- CSF, CNS, pericardial fluid, bronchial secretions, middle ear
71
what are the 2 proteins that bind drugs and what types of drugs do they both bind
- albumin: acidic drugs
- A-glycoprotein: basic drugs
72
where do drugs accumulate in tissue
- organs
- muscle
-adipose
- bone
73
what is an exmaple of a drug that accumulates in adipose tissue
fentanyl
74
what is an example of a drug that accumulates in bone and what does this cause
tetracycline- causes staining in the teeth
75
what is redistribution and what is an example
- from site of action into other tissues or sites
- propofol
76
describe the distribution in the CNS
- blood brain barrier exists
- efflux transporters
- inflammatory processes
77
what is the volume of distribution
volume of fluid in which a drug would need to be dissolved to have the same concentration in plasma
- not a real volume
78
volume of distribution is the relationship between:
dose and resulting Cp
79
what drugs tend to have a larger Vd
lipophilic drugs
80
what drugs have a lower Vd
protein bound drugs
81
where are drugs found with a Vd of more than 5 L
confined to plasma
82
where are drugs found that have a Vd of 5-15L
distributed to extracellular fluid (RBCs and plasma)
83
where are drugs found that have a Vd larger than 42 L
distributed to all tissues in the body especially adipose
84
increased Vd = _____ likelihood that the drug is in the tissue
increased
85
decreased Vd = _____ likelihood that the drug is confined to the circulatory system
increased
86
drugs are removed either:
metabolized/biotransformed and eliminated or excreted unchanges
87
drugs must be _______ to be removed
water soluble
88
lipid solubility is good for _____ and bad for ______
absorption and distribution; excretion
89
what does biotransformation do
converts drugs into polar metabolites
- lipophilic into hydrophilic
90
what does the liver accomplish metabolism of drugs through
P-450
91
where is the cytochrome P-450 system locatde
liver, kidney, intestines
92
what are the main most common cytochromes in the cytochrome P-450 system
- CYP 3A4
- CYP 2D6
- CYP 2C9
- CYP 1A2
93
describe phase 1 of metabolism
- catabolic
- exposes functional group on parent compound
- usually results in loss of pharmacologic activity
- activation of prodrugs
94
what is an example of a prodrug that is activated in phase 1 of metabolism
fosphenytoin to phenytoin
95
what are the possible interactions with P450
- substrates
- inhibitors
- inducers
96
what is an example of a substrate in the P450 system
warfarin
97
what is an example of an inhibitor in the P450 system
bactrim
98
what do inducers in P450 do
the drug sends a message to the nucleus to make more CYP protein which lowers the concentration of another drug thus decreasing that drugs efficacy
99
describe the genetic polymorphisms of the CYP isoenzymes
- great genetic variability in function
- may be poor metabolizers or rapid metabolizers
- this can lead to subtherapeutic effect such as codeine and tramadol
- or this can lead to toxicity such as in diazepam, alprazolam
100
describe phase 2 of metabolism
- occurs after functional groups are exposed
- anabolic: adds water soluble molecules to structure
- much less inter- patient variability
101
what are the major reactions in phase II of metabolsim
- glucuronidation
- glutathione conjugation
- sulfate conjugation
- acetylation
102
what are the primary routes of excretion
kidney, lung and feces
103
what is excretion
- removal of an unchanged drug
- polar compounds -> lipid soluble compounds
104
what are the 3 processes of excretion in the kidneys
- glomerular filtration
- active tubular secretion
- passive tubular reabsorption
105
describe the process of excretion in the kidneys
- dependent on renal function
- only unbound drug filtered
- non-ionized weak acids and bases are passively reabsorbed
- alkaline urine traps ionized acidic molecules and increases excretion
106
describe excretion through the lungs and what is it affected by
- primarily inhaled anesthesia or volatile liquid
- affected by respiratory rate and blood flow
107
describe excretion through feces
- unabsorbed orally administered meds
- metabolites excreted in the bile
- un-reabsorbed metabolites secreted into the intestinal tract
108
what is the main factor that determines rate of passive transport
lipid solubility
109
how many molecules bind per molecule of albumin
2
110
extensive protein binding can _____ drug elimination
slow
111
competition for protein binding can sometimes lead to:
interactions
112
which protein is more commonly bound
albumin
113
acids get trapped in ____ environments
basic
114
gut absorption depends on factors such as:
- GI motility
- GI pH
- particle size
- interaction with gut contents
115
what catabolic reactions take place in phase I of metabolism
oxidation, reduction, hydrolysis
116
which phase of metabolism results in more active products
phase I
117
which phase of metaboslim involves the P450 system
phase I
118
what is the end result of phase II metaboslim
conjugated, inactive and polar products for excretion
119
unless they're protein bound most drugs are filtered through:
the glomerulus
120
weak acids and bases are actively secreted into:
the renal tubule
121
lipid soluble drugs are ______ not efficiently excreted
passively reabsorbed
122
