Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
266 Cards in this Set
- Front
- Back
The extent of ionization of a drug is important since generally the UNCHARGED form of a molecule is
|
the form permeating membrane
|
|
What are the water-soluble forms
|
ionized
|
|
What happens when a drug is TOO water-soluble
|
cannot more from stomach to circulation
|
|
HA====H+ + A-, the farther this equilibrium lies to right
|
STONGER the acid is
|
|
Anything stabilizing A- (more H's) will shift the equilibrium to
|
RIGHT increase acid strength
|
|
How do substutents affect the acidicty of aliphatic acid such as CH3-COOH then ClCH2COOH
|
make more acidic
|
|
Activity of sedative adn hypnotic agents are depend upon
|
ADME
|
|
For absorption and elmination, must drug have polar and non-polar functionalilty
|
YES
|
|
For metabolism/elimination 3 alcohol comparted to 1 alcohols for sedative/hypnotic agents
|
3 alcohols are longer lived
|
|
For metabolism of sedative/hypnotic agents what are 2 ways are longer lived
|
3 alcohols
Amides |
|
Which live longer for sedative/hypnotic agents (amides or esters)
|
AMIDES
|
|
Aldehydate put in water form
|
hydrate in water
|
|
What is 1st sedative hypnotic
|
tricholoracetaldehyde
|
|
With most aldehydes the hydrate is
|
a non-isolable product in equlibirum with aldehyde
|
|
Which is more polar choloral hydrate or trichloroacetaldehyde
|
hydrate
|
|
When an alcohol is added to an aldeydate what is formed
|
hemiacetal
|
|
When 2 alcohols are added to an aldehyde what is formed
|
acetal or chloral diethyl acetal
|
|
Which is the most lipid-soluble in Tricholoracetaldehyde reaction
|
acetal
|
|
What compoents distrubtes more readily to brain and more potent sedative
|
chloral diethyl acetyl
|
|
What is the active metabolite of chloral
|
trichloroethanol
|
|
What is the inactive metabolite of of chloral
|
trichloracetic acid
|
|
3 Acetaladehyde will spontaneously
|
trimerize on standing
|
|
How can one obtain an aldehyde from a trimer or paraldehyde
|
heat solution
|
|
Ethanol is a sedative, but POOR, it requies a large dose and is rapidly metabolized, the potenct of ethanol can be imporved by
|
making is more lipophilic and less susceptible to metabolism
|
|
How can ethanol be made more lipophilic and less susceptible to metabolism
|
Increase the number of carbons to 7, adding a carbon-cabon-carbon double bond, adding a halogen (CL), and making a primary alcohol a 3 alcohol
|
|
What is the result of increasing # of carbons to 7, adding a carbon-carbon double bond, adding a halogen (CL), and making primary alcohol tertiary
|
ethclorvynol
|
|
Barbiturates were developed in 1900s after chloral, and are derivates of
|
barbituric acid
|
|
What type of receptors does barbiturates interact with
|
gaba/chloride ionophore complex
|
|
How many acidic hydrogens are there is barbuturic acid
|
2
|
|
The hydrogens at what position in barbituric acid are most acidic
|
at C5- and ionization is resoance-stabilized PKA 4
|
|
What is the pka of the hydrogens at N3
|
much less acidic pka 7
|
|
What must barbiturates be to enter the CNS
|
50% unionzied to enter CNS
|
|
If Barbiturates must be 50% unionized to enter CNS, what acidic hydrogens must be replaced by other substutents
|
both hydrogens at C5
|
|
Activate barbiturates must be
|
5,5 disubstiuted
|
|
Are barbiutates (sedative/hynotic) stable in aqeous base and form
|
NO Carbonyl and 2 NH2, and 2 CO2 connected together
|
|
Is barbituate itself chiral
|
NO
|
|
Barbiturates duration of action is a function of
|
lipid solubility
|
|
At 5th carbon of barbiturate adding 4-6 carbons does what
|
more water-soluble duration of 8-12 hours
|
|
At 5th carbon of barbiturate adding 6-8 carbons does what
|
more lipid soluble duration 6-8 hours (SHORTER DURATION OF ACTION)
|
|
More lipophilic barbiturates have
|
a shorter duration of action
|
|
What happens are C5 when there is >10 carbons
|
convulsant
|
|
Can there be a H at 5th carbon
|
NO
|
|
What would give a barbiturate an ultra-short duration of action
|
a Thioketone, at C2
|
|
Longer acting barbiturates are more
|
water-solulbe
|
|
Mephobarbital is rapidly...
|
N-demethlylated to phenobarbital
|
|
Is P-hydroxylation of mephobarbital enantioselective (have STEROCHEMISTRY
|
YES-all para-hydroxylation has steriochemistry
|
|
What effect does a benzene ring have on a barbiturate at C5
|
benze forms pie clouds above and below plane, and benze b/c polarized induced dipole
|
|
Benzene forms a pie cloud above and below plane, so beneze b/c
|
A polorized induced dipole--makes more water soulbe
|
|
Barbiturates unergo what type of metabolism
|
extensive hepatic metabolism
|
|
What is common metabolism method of CYP450 on phenobarbital
|
para hydroxylation (adding of an OH to aromatic ring
|
|
Does any oxidation to barbiruates destory activity
|
YES
|
|
Benzodiazepine were discovered accidently looking for new
|
methaqualone analogs
|
|
Benzodiazepines were 1st drugs availbable for treatment of
|
anxiety
|
|
Receptor site of Benzodiazepines
|
gaba/chloride ionophore complex (GABA-A)
|
|
Do benzodiazepines have ionizable portions like barbituares
|
NO
|
|
Are benzodiazepines water soluble
|
very little water soluble
|
|
If a benzodiazepines are SO WATER INSOLUBLE, how are they absorbed
|
the gut has a large SA so eventually absorbed
|
|
Diazepam can be broken down into
|
Temazepam and FAST nordiazepam
|
|
Diazepam rapidly b/c nordiazepam, what is benfit
|
Has no hydroxy 3--so UNDERGOES VERY SLOW metabolism to oxazepam (40hrs)
|
|
Temezaepam then is converted into
|
oxazepam by N-demethlayyion
|
|
What is duration of action of oxazepam
|
short DOA, undergoes glucuronide and becomes glucuronide
|
|
What are CYP450 of benzodiazepines
|
CYP 1A2, CYP3A4, CYP 2C9 and 2C19
|
|
All benzodiazepines, with extensive CH3 at C1 become
|
nordiazepam by N-dealkylation and have LONGER DOA
|
|
What do all short acting benzodiapines have
|
a hydroxyl at C3
|
|
Flunitrazepam is AKA, and properties
|
Date-rate drug with a nitro group and F--makes lipid soluble and RAPID onset of action
|
|
The nitro goup of flunitrazepam is RAPIDLY
|
reduced to an amino group and acetylated
|
|
What are 2 ways Benzodiazepams undero metabolism
|
N-demethlation and C3 oxidation
|
|
Where do barbiurates undergo metabolism
|
C5--of beneze ring or alkyl chain oxidation
|
|
Triazolam is rapidly alpha hydroxlated to waht
|
a partially active intermediate by CYP3A4
|
|
What is a non-benzodiazepine Gaba-A agonists
|
Zolpidem (ambien), zoleplon (sonata), and eszopiclone (lunesta)
|
|
What is Zolpidem
|
an imidazopyridine
|
|
What is pka of Zolpidem and onset of action
|
6.2 adn rapid absoprtion
|
|
What type of metabolism does Zolpidem undergo
|
benzylic oxidation,
|
|
After Zolpidem undergoes benzylic oxidation, to a primary alcohol, what happens
|
Alcohol dehydrogenase oxidation to finally a carboxylate
|
|
What is zaleplon
|
a pyrazolopyrimidine
|
|
What is eszopiclone (lunesta)
|
a cyloprrolone
|
|
Do anticonvulsants bear great structual similairty to
|
barbituates
|
|
The discovery of what in the 1970's helped explain why we have morphine receptors
|
peptides
|
|
What what the model that orinally proposed morphine receptors
|
Beckett model
|
|
Endogenous opiate agoinsts arise from
|
processing of large precursors
|
|
What is the principal constituent of opium
|
morphine
|
|
What is opium
|
dried exudate of Papaver somniferum
|
|
Morphine was isolated in 1805, and was first
|
alkaloid
|
|
Only one enantiomer of morphine is
|
active
|
|
How many rings is morphine
|
5
|
|
What are locations of Morphine modifcations
|
3 OH, 6 OH, 7-8 double bond, 14-OH addition, and 17N-subsititution
|
|
What metabolism does Codiene undergo
|
O-demethylation to morphine (active metabolite)
|
|
What is inactive metabolite of MORPHINE/codeine
|
the product from N-demethylation by CYP3A4
|
|
Alterations of Morphine 3-OH makes
|
codiene
|
|
Reduction or remove of Morphine 7,8 double bound does
|
reduction increases potency, less chemically reactive
|
|
What is a reduction in 7,8 double bond make less chemically reactive
|
removal of allylic alcohol
|
|
Reduction of morphine 7,8 double bond is used in conjunction with
|
oxidation of 6-OH
|
|
Heroin is very lipid soluble, and is radidly hydolyzed by an esterase to
|
6-acetlymorphine
|
|
Is 6-acetylmorphine found in poppie seeds
|
NO
|
|
What type of additiove liability is heroin on 1st use
|
50%
|
|
What is esterased first in heroin
|
3-ester to OH, and carboxcilic side product
|
|
HEROIN is rapidly metabolized, in heroin fatalites where is it found
|
stomach contents
|
|
Morphine is metbolized into morphine 6B-glucuronide is this active as well
|
YES
|
|
Morphine 6B-glucuronide is 1000 flod more potetn than morphine but
|
doesnt enter CNS well, and is rapidly excreted in urine
|
|
Reducing double bond of 7-8, and add ketone to 6-OH does what to morphine
|
more potent than morphine, not as reactive, less polar so better CNS distribution
|
|
Addition of OH-14 does what
|
makes oxycodone which is more potent
|
|
Why is oxycodone uniquely potent
|
more POLAR and unlike others accumlates in brain
|
|
Changes where on morphine increase potency
|
removing 7,8 double bond
adding ketone 6-OH addtion of OH14 |
|
What do you 17N-substitute
|
allyl
|
|
What does 17N-substitution do
|
mew-receptor antagoinst---throws patietn into withdrawl
|
|
What is oripavane
|
synthetized by diels-alder reaction to create a 6 membered ring
|
|
Changing the N-methyl substutent to an ally produces what
|
a powerful mew-antagoinst
|
|
What is use of Pentazocine
|
Kapa-agoinst--too many side effects for useful pain contorl
|
|
The enatiomers of Levophanol and Dextromethorpahn, which is inactive
|
dextromethorphan
|
|
What changes can you make to phenylpiperidines
|
N-phenylethyl substituion
|
|
What does a N-phenylethyl substitution do, example
|
creates a very potent- u-agoinsts--fentanyl
|
|
What happens when you add very large N-substituents to phenylpiperidines
|
limit CNS distribution--and works in GUT...GUT is one giant u-receptor
|
|
What are benifits of methadone
|
good bioavailability and maintenance of addicts
|
|
What is the active metabolite of methadone
|
methadol (ketone to alcohol)
|
|
How does tramadol b/c active
|
O-demethylation by CPY2D6
|
|
What happens to tramadol with individuals who lack CYP2D6
|
diminished pain relief
|
|
What is pka of tramadol
|
pka 9
|
|
Is tramadol more potent than morphine
|
nO
|
|
What is Butorphanol
|
strong K-agoinst and u antagoinst- with 5x activity of morphine (will casue withdrawl) Must be take IM--no oral bioavailability
|
|
Is Buprenorphine more potent than morphine
|
YES 20-50 mroe potent
|
|
If Buprenorphine is 20-50 X more potent why can it only produce ED50 alagesic effect of morphine
|
parital K-and u agoinst
|
|
Why can't Buprenorphine be taken orally--NO ORAL BIOAVAILABILITY
|
rapid 3-O glucuronidation
|
|
Is Naloxone an effect u-antagoinst to Buprenophrine
|
NO--Buprenorhpine binds to u receptor to STRONG
|
|
Benefits of Buprenorphine being a partial agoinst
|
cannot produce the tolerane adn addication of full u agoinsts
|
|
What emerged from antihistamine research
|
antipsychotics
|
|
What was first antipsychotic
|
CPZ chlorpromazine
|
|
What class is CPZ
|
Phenothiazines
|
|
What is required for phenothizaine
|
MUST be an EWG at C2
A 3 carbon chain with no braching |
|
WHat happens to a phenothizaine with no EWG
|
NO ACTIIVTY
|
|
How do you increase the potency of phenothiazines
|
inrease the size of the N-substiutent
|
|
What type of receptors do phenothizaine interact with
|
dopamine receptor
|
|
How do you make phenothizaine water-soluble for injection
|
STONG di-acid
|
|
What is a very strong di-acid
|
ethanedisfulonic acid
|
|
What is prepared with piperazine-containing phenothiazine
|
bis-sulfonate salt of piperzine
|
|
The duration of action of a phenothizine can be increase with what type of phenothiazines
|
phenthiazines with ending with a free hydroxl
|
|
What happens to Perphenazine as it ends with a free hydroxyl
|
by esterfication with a long fatty acid chian
|
|
Esterfication of phenthiazine can serve as a
|
Sustained release form
|
|
What types of phenothizaines can be modified
|
ending in OH
or have piperazine |
|
What are possible metabolisms of CPZ
|
N-demethlation
S oxidation to sulfoxide or sulfone hydroxylation |
|
What are steroisomers of thioxanthenes
|
cis and trans
|
|
What do thioxanthenes give rise to
|
geometric ISOMER--only cis is active
|
|
Must the butyrophenone be kept intact
|
YES
|
|
Property of Butyrophenones
|
very lipid soluble
|
|
What amino acid plays a role in DA receptor binding of protanted amine
|
aspartate
|
|
What receptor binding points for antipyschotics with 2 rings
|
interact with pi-pi stacking interactions
|
|
How do Butyrophenone interact with pi-pi stacking
|
ring--pi-pi stacking, electron interactions with carbonyl oxygen
|
|
Receptor modeling has been done using a DA receptor agoinst AKA
|
8-OHDOPAT
|
|
How many transmembrane segemtns are there with angoinst binding
|
7
|
|
What does Phenol bind to
|
hydrogen bonds to OH of serine 193
|
|
What does Phenyl bind to
|
pi-pi stacking with phenylalanine 390
|
|
What does Amine bind to
|
ionic interactions to aspartate
|
|
How do local anesthetics work
|
block sodium channels and AP
|
|
Sodium channels consits of a tetramer of units, with each having 6 transmembrane segments, where does local anesthetic bind
|
6th segment of the fourth unit
|
|
What is problem with cocaine
|
Labile ester rapidly hydrolzed
CNS--abuse problems Vasoconstriction |
|
Early research determines that only a portion of cocaine strucutre is needed for local anesthesia that is
|
aromatic ring
conjugated ester intermediate chain terminal amine |
|
1st local anestestic derived was, and effects
|
procaine--vasodialtor
|
|
What are 4 main things needs for structure/relationship of anestethics
|
(aromatic ring) lipophilic
Conjugated ester intermediate chain polar portion (amine) |
|
The intermediate chain needs to be
|
2 or 3 carbons can be branched
|
|
The polar portion is usually an amine, it is usually
|
teriatry amine
|
|
Local anesthetic activity increases with
|
increasing lipid of polar end (making an isobutyl)
|
|
What are 2 topical anesthetics only
|
benzocaine and butamben
|
|
How do you make a topical anesthetic
|
removed terminal amine--ester with 3 carbons
|
|
Procaines and esters--could not be sterilzed, so what was developed that is stable in boiling water
|
amide anestetheics---lidocaine
|
|
What are benefits of amide anesthethetics (lidocaine)
|
faster onset of action---and decrease chemical reactivity--longer DOA
|
|
What is lidocaine metabolized by
|
amidase
|
|
How can lidocaine be metabolized
|
Oxidation or methyl group
N-dealkylation |
|
NO is a gas rapidly destroyed by
|
Oxygen
|
|
How is NO stored
|
S-nitrosylmeyhionine
|
|
Nitrous acid + alcohol=
|
nitrite ester
|
|
Nitric acid + alcohol=
|
nitrate ester
|
|
Organic nitriies seve as a source of
|
NO by ONE electron reductase
|
|
Organic nitrates are reduced to
|
nitrous acid by 2 electron reduction
|
|
RONO2 =
|
ROH + HONO
|
|
RONO -
|
ROH + NO
|
|
What is the only stereochemical nitrate
|
isorbidie dinitrate
|
|
Isosorbide dinatrate has 2 nitro groups, one is acessible, but inaccessible one
|
provides a longer duration of action
|
|
Sodium nitropursside is
|
a source of NO
|
|
What does NO binds to
|
F3+3
|
|
Sodium nitropursside NO comes off easily, replaced by
|
NO replace by water
|
|
What are 3 chemical approaches to lower BP
|
1. CNS
2. PNS 3. Renal mechanisms |
|
What are 2 drugs that works by CNS mechanisms
|
1. Aldomet
2. Clonidine |
|
Alodmet was designed as, Aldomets goal
|
an inhibitor of DOPA decarboxylase--goal to delete peripheral CCA
|
|
Aldomet, is a perihperal dopa decarboxylase inhibit that does what
|
enhances the CNS effect
|
|
alpha-methyldihydroxyphenylalanine is AKA
|
Aldomet
|
|
What is a zwitterion at pH 7.4
|
Aldomet
|
|
Aldomet is converted into
|
alpha-metyldopamine
|
|
Alpha-mehthyldopamine is convereted into
|
alpha-methylnorepeine
|
|
Alpha-methylnorepinephrine is a false transmitter--how does it act centrally
|
hypotensive agent
|
|
Clonidine is dervided from
|
guanidine
|
|
What is PKA of clonidine
|
8.25
|
|
What is optimal placement of clonidine
|
2,6 optimal placemet
|
|
What is optimal EWG for clonidine, can you can chain length
|
CL (alkyl or bromo substituion bad--no clonidine is optimal
|
|
What are changes that can make clonidine worse
|
1. Alter CL placement
2. Use another substituent 3. Increase chain length 4. Change N-ring size |
|
What is optimal N-ring size for clonidine
|
imidazole
|
|
What is benefit of CL
|
makes lipophilic, and prevent imidzoline rotation,
|
|
What is benefit of phenyl in clonidine
|
phenyl decrease basicity of guanidine from 13 to 8
|
|
What can't you change the chain length of clonidine
|
chain length is critical to spatial match NE
|
|
What are peripheral mechanisms for reducing BP
|
1. Ganglionic blocking drugs
2. Reserpine 4. Guanethidine |
|
What are properties of Ganglionic blockers
|
permenant cations, water soluble, no oral bioavilability, and rapidly filtered
|
|
No sutrucutral permutaitons work is RESERPINE, irrervesible after
|
24hrs
|
|
What do you need to do to recover from reserpine
|
make new vesicles
|
|
Does hydrolysis make reserpine inactive
|
YES
|
|
Guanethidine is essenetialy
|
a permant cation
|
|
How many N are protanted at a time on Guanethidine
|
ONlY ONE
|
|
ACE is an enzyme that contains
|
Zn+--similar to carboxypetidase
|
|
ACE converts
|
Angiotension I (10aa) to Angiotensin II (8aa)
|
|
What was the first ACE inhibitor
|
captopril
|
|
What does captorpil contain
|
SH, which binds to zinc tightly
|
|
What are the 3 componenets of ACE enzyme
|
HIS-ZN+, Tyr--OH and Arg NH3+
|
|
What does Enalprilat bind better than captopril to ACE (enzyme)
|
mimics that Transition state of Angiotensin I
|
|
How does enalaprilat mimics the angiotensin I transition state
|
has a tetrahydreal carbon
|
|
What does ZN coordinated
|
the carbonyl to be hydrolyzed
|
|
Enalaprilat has very poor bioavailability, how is this fixed
|
pro-drug-enalapril--has an ester
|
|
CCAs are NT released upon stimulation of the
|
sympathetic nervous system
|
|
What are the major CCAs
|
NE, Epi
|
|
What is Flight or fight response
|
increase HR, BP, blow flood to skeletal muscle
|
|
CCA are very polar do they esaily distrubte to CNS
|
NO
|
|
Where are CCAs synthetzied
|
central and perihperna nerve ending, and adrenochrmaffin cells
|
|
What is percursor for CCAs that is transported into CNS for synthetsis
|
synthetisis
|
|
Where are cCA stored
|
vesicles, and chromaffin cells
|
|
Action of CCAs is terminated by what
|
uptake
|
|
What are CCAs very sensitive to
|
chemical oxdiation to ortho-quinonones
|
|
Are ortho-quinonones active
|
NO--inactive as NT
|
|
Tyrosines is transported into CNS, the rate limiting step is
|
Tyrosine hydroxylase
|
|
Tyrosine is meta-hydroxlated to
|
DOPA
|
|
Within the storage vesicle, what happens
|
DA is beta-hydroxylated to norephine
|
|
The hydroxyl group of NE has sterochemsitry in what configuartion
|
R configuration
|
|
NE b/c Epi through
|
Phenylethanolamine N-metyltransferase
|
|
Where does converstion of NE-to EPI occur
|
adrenal chromaffin cells
|
|
CCAs exsacping neuronal uptake are metabolized by
|
MAO
COMT Aldehyde reductase ALdehyde dehtdrogenase |
|
What are CCA interactions with B receptors
|
Cateocols interact with Serine hydrogen, and protanted amine interaacts iwth aspartate,
|
|
WHat does MAO do
|
converts primary amines to aldehydes
|
|
What does COMT do
|
methlates the OH groups of meta
|
|
NE b/c what with MAO
|
DOPGAL
|
|
NE by COMT b/c
|
normetanephrine
|
|
What does ALdehyde reductase do
|
aldehyde b/c alcohol
|
|
What does Aldehydye DEHYDOGENASE DO
|
aldehyde to carboxylic acid
|
|
What are the 3 adrenegric receptor substyes according to
|
NE, E and isproteneronol
|
|
Alpha preferance
|
EPI >NE >ISO
|
|
Beta preferance for
|
ISO>EPI>NE
|
|
What happens are size of N-substituent increases
|
Beta activity increases due to a lipophilic binding pocket (alpha decreases)
|
|
Phenylethanolamines is general sturucure for ALL adergergic AGOINST
What happens when you add a methyl R2 of phenylethanolamine |
slows down action of MAO
|
|
What ring substitution is best for both alpha and beta agoinst
|
3,4 dihydroxy substitution
|
|
What happens if you only have a 3-OH
|
alpha activity is reduced, and Beta activity nearly eliminated
|
|
What are 3 alpha agoinsts
|
phenylephrine, metaraminol, and methoxamine
|
|
WHat are main characteristic of alpha agoisnt
|
3-0H, and small N-substitutent
|
|
When there is no aromatic hroxyls, agoinst actity may be
|
mixed (direct/indirect) or indirect
|
|
What are 2 properties of Al agoinst
|
little cardic stimulation, and not substrates for COMT--so longer acting the NE
|
|
How is methoxamine bioactivated
|
O-demethlation
|
|
What is another class of Al agoinst
|
the aryl-imidazolines
|
|
Main action of A1
|
vasoconstrtion
|
|
Do alpha receptors accept more strucutally diverse agoisnts
|
YES
|
|
What are characteristic of the aryl-imidzolines (oxymethazoline and xylometazoline)
|
contain a lipophilic region on aromatic ring usually ortho--or
|
|
What is required for activty of alyl-imidazoles
|
lipophilic functionality on the aromatic ring
|
|
What are B2 agoinsts
|
Bitolterol
Ritodrine Albuterol Terbutaline Pirbuterol |
|
What makes B2 agoinsts NOT SUBSTRATES for COMT
|
methyl addition in catechols
|
|
Catecol-containing compounds are rapidly metabolized by COMT--what can make more resistant to COMT
|
alterations to catecols (addition of methyl
|
|
What are Alpha agoinsts not substrates for COMT
|
do not have catechols
|
|
What makes the aryl-imidaolines alpha ANTAGOINSTS
|
they are missing the aromiatc lipophilic substitute or methylene bride connecting imidzoline ring
|
|
What is a non-selective B antagoinst
|
propranolol
|
|
What makes propranolol
|
isoproternol with an addition of an ether linkage
|
|
What does an ether linkage causes
|
nonselective B-antagoinst
|
|
How do you make a selective B1 antagoinsts
|
Ether linkage with a para substitution
|
|
What is base of Beta antagoinst
|
isoprotenetol--added ether linkage
|
|
More lipophilic somthing is how is cleared
|
by liver
|
|
The more water soluble soble somthing is
|
is more likely filtered by kidneys
|