Drugs which have a mechanism of action dependent on enzyme inhibition include
pargyline
false
isocarboxazide
halothane
physostigmine
fieldformat
DFP is a phosphorous anticholinesterase. Its proper name is diisopropylfluorophosphonidate which is why it is normally called DFP or dyflos. Potent, long-lasting irreversible, absorbed through the skin, non-competitive. Pargyline and isocarboxazide are MAOI of the hydrazine type. They are long-lasting and non-competitive. Physostigmine is an anticholinesterase (also called eserine). It is found in the African Ordeal Bean (totally useless information). Reversible, of short duration, combines with anionic site. Halothane is a volatile general anaesthetic. It may inhibit some enzymes in high concentration but this is not thought to be an essential part of its mechanism of action.
Explanation none
level
A3:30
Biotransformation of sulphonamides
is mainly by acetylation of the para-amino group
may result in metabolites of low water solubility
false
produces metabolites with no appreciable antibacterial activity
is the only mechanism which terminates their action
fieldformat
shows genetic polymorphism
The biotransformation of sulphonamides involves the acetylation of the free amino group which is essential to their activity. This also lowers their solubility and hence the risk of crystaluria and kidney damage from the acetylated products. Actions are sometimes terminated by excretion as extent of acetylation varies greatly from compound to compound.
Explanation none
level
A3:31
Ribosides are formed by
purines
pyridine
pyrimidines
level
pyrroles
fieldformat
pyrenes
false
false
false
Ribosides are the biotransformation products of bases similar to those found in DNA and RNA.
Explanation none
A3:14
SFrame
:PHYSSIZE
sframe
sframe
Probable biotransformation pathways for aspirin include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
false
Look at the functional groups. Note species variation is considerable. phenyl ring is hydroxylated and the OH group acetylated. The carboxyl is also attacked to a small extent.
Explanation none
A3:19
SFrame
:PHYSSIZE
sframe
sframe
Possible biotransformation pathways for amphetamine include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
MAO. No catechol groups thus COMT inactive. Look at functional groups. Phenyl ring hydroxylated. Nitrogen is dealkylated.
Note that deamination is very slow because of the alkyl group on the alpha carbon of the sidechain.
Explanation none
A3:16
Probable biotransformation pathways of morphine include
hydrolysis
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
false
Think about the functional groups.
The nitrogen and oxygen are demethylated and glucuronides are formed.
The phenyl ring is not usually attacked.
Explanation none
A3:17
Probable biotransformation pathways for adrenaline include
hydroxylation
dehalogenation
false
false
dealkylation
deamination
fieldformat
methylation
MAO & COMT. Think about the functional groups. Note taken up by uptake 1.
Catechol OH is methylated (catechol-O-methyl-transferase).
Dealkylation and deamination both take place (particularly the latter by
monoamine oxidase).
Explanation none
level
A3:18
Probable biotransformation pathways for chlorpromazine include
hydroxylation
dehalogenation
false
dealkylation
deamination
fieldformat
methylation
Think about the functional groups.
Phenyl ring hydroxylated.
Chlorine removed (dehalogenation).
Nitrogen dealkylated.
Nitrogen also deaminated.
Explanation scrolling
level
A3:20
Probable biotransformation pathways of halothane [CF3.CHBrCl] include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
false
Dehalogenation removing Br, Cl & F in that order.
Note that biotransformation in low oxygen tension may be different and may give rise to toxic materials which cause the jaundice associated with halothane use.
Explanation none
A3:21
Probable biotransformation pathways for diazepam include
hydrolysis
dehalogenation
false
false
dealkylation
deamination
fieldformat
methylation
Think about the functional groups and the clinical importance
of biotransformation productsof theis benzodiazepine.
Chlorine removed (dehalogenation).
Phenyl ring hydroxylated.
Nitrogen dealkylated.
CONH2 (amide) hydrolysed.
Explanation scrolling
level
A3:22
A proximate carcinogen is
a non-toxic metabolite of a carcinogen
a compound which is biotransformed into a carcinogen
a compound which gives rise to cancer
level
a compound which may be oxygenated
fieldformat
a compound which gives rise to secondary cancers
false
false
false
A pro-carcinogen (eg.naphthylamine) is metabolised (eg. hydroxylation) to a material which produces cancer (naphthylhydroxylamine). Proximate carcinogen or proximate oncogen has been used to describe either of these materials & the term is probably best avoided. Remember also to distinguish between promoter (co-carcinogen) and initiator.
Explanation none
A3:22
A3:26
A3:23
Polarisation
is a property peculiar to halogens
is more likely to occur with fluorine than iodine
is dependent on the size of the atom
level
involves the movement of protons
fieldformat
is proportional to electronegativity
false
false
false
false
Polarisation is a phenomenon in which the outer (valency) electrons can be shifted causing the co-valent linkage to weaken. The further the electrons from the nucleus (bigger the atom) the more polarisable the atom.
Explanation none
A3:23
A3:24
Codeine is metabolised by
O-demethylation
N-demethylation
S-demethylation
level
P-demethylation
fieldformat
C-demethylation
false
false
false
Think about the functional groups.
Note some morphine is produced.
Mainly O and N demethylation.
There is no S or P in this drug.
Explanation none
A3:24
A3:25
Type 1 substrates of cytochrome P450-dependent hydroxylases
include acetanilide
include hexabarbitone
false
false
are hydroxylated faster than type 2
are all barbiturates
fieldformat
all give similar spectral changes
Type 1 and type 2 substrates give different spectral shifts:
1 from 420 to 415 and 2 from 420 to 426.
Note that the spectra for these figures are difference spectra.
Explanation none
level
A3:25
A3:26
NADPH is derived from
nicotine
nicotinamide
false
adenine
nicotinic acid
ribose
fieldformat
Nicotine is a toxic alkaloid found in tobacco
Explanation none
level
A3:27
The supply of reducing power for drug biotransformation
is metabolically expensive
is effectively unlimited
false
false
depends on glucose metabolism
goes via NADH
fieldformat
involves FADH2
NADPH is produced by the pentose phosphate pathway which involves using G-6-phosphate to generate reducing power (not ATP). Hence it is energetically expensive and limited.
Explanation none
level
A3:28
NADPH is produced
as a biosynthetic reducing agent
from NADH
from glycolytic reducing power
level
from the pentose phosphate pathway
fieldformat
from nicotine
false
false
false
NADPH is produced by the pentose phosphate pathway which involves using G-6-phosphate to generate reducing power (not ATP). Hence it is energetically expensive and limited.
Explanation none
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Biotransformations
Dental Students
Medical Students
Science Students
level
Select
The smooth endoplasmic reticulum of the liver is concerned directly with the
synthesis of urea
synthesis of haem
synthesis of cholesterol
level
synthesis of protein for extracellular use
fieldformat
formation of glucuronide conjugates
false
false
false
As well as catalysing drug biotransformation, the smooth endoplasmic reticulum forms cholesterol & glucuronide conjugates.
Explanation none
A3:10
A3:18
The enterohepatic shunt may involve
the enzyme beta-glucuronidase
active secretion into the bile
drugs such as phenolphthalein
drugs such as chloramphenicol
fieldformat
the prolongation of drug action
The enterohepatic shunt often involves drugs which are excreted in bile as glucuronides, hydrolysed in the gut by glucuronidase and then reabsorbed to be recycled through the process again.
Explanation none
level
The principal mode of biotransformation of
sulphonamides is N-acetylation
benzene is oxidation to a phenol
false
pentobarbitone is oxidation to an alcohol
noradrenaline is N-dealkylation
fieldformat
atropine is hydrolysis of an ester link
Sulpha drugs metabolised in kidneys by N-acetyl-transferase. The acetyl- sulphonamides are less soluble in urine than the parent drugs and may crystalise out (hence drink a lot when on sulpha drugs). Benzene is biotransformed by liver hydroxylases. Pentobarbitone and many other barbiturates, is biotransformed by oxidation of the alkyl chain on the C5 carbon of the ring. There are no removable alkyl groups on the nitrogen of NA. COMT and MAO O-methylate ring hydroxyl and deaminate respectively. Atropine is hydrolysed by any esterase. Note rabbits have a very effective plasma esterase and hence can eat deadly nightshade safely.
Explanation none
level
The principal mode of biotransformation of
succinylcholine is hydrolysis of an ester
chloral hydrate is reduction to an alcohol
cocaine is hydrolysis
procaine is hydrolysis of an ester
fieldformat
benzoic acid is conjugation with glycine or glucuronic acid
Look at the drugs functional groups. Plasma esterases make succinylcholine very short acting (5 min) except in patients with an abnormal esterase where duration can be up to 30 min.
Trichloroethanol is the active sedative material. Procaine is hydrolysed at the ester link.
Note that substitution of an amide link makes a much longer lasting drug which is used as an antidysrhythmic (procainamide).
Explanation none
level
Procaine is biotransformed in the body to
para-amino-hippuric acid (PAH)
para-amino-benzoic acid (PABA)
benzene
level
dimethylamine
fieldformat
diethylaminoethanol
false
false
false
Hydrolysis of the ester link by plasma cholinesterase. Note that PABA is produced which may antagonise the anti-bacterial action of sulphonamides. Procainamide (where the ester link in procaine has been replaced by amide) is longer lasting and is used as a treatment for some cardiac dysrhythmias. Class I anti-dysrhythmic.
Explanation none
The following could correctly be called prodrugs
prontosil
liquid paraffin
false
false
castor oil
chloral hydrate
fieldformat
phentolamine
A prodrug is a material which is biotransformed to an active substance.
Castor oil to ricinoleic acid by ester hydrolysis
Chloral hydrate to trichloroethanol by hydrolysis.
Prontosil was one of the early dyes which were used as antibacterials by
Erlich and is infact active because it is biotransformed to a sulpha drug.
Phentolamine is an alpha-adrenoceptor blocker. Liquid paraffin is used
occasionally as a laxative (usually in assoication with magnesium
hydroxide).
Explanation scrolling
level
The following could correctly be called prodrugs
disulfiram
L-dopa
false
false
cyclophosphamide
streptomycin
fieldformat
diphenhydramine
A prodrug is a material which is biotransformed to an active substance. Disulfiram to diethyldithiocarbamic acid by -S-S- bond reduction.
L-dopa to dopamine by dopa decarboxylase (L-aromatic aminoacid decarboxylase).
Cyclophosphamide to ketocyclophosphamide by oxidation.
Streptomycin is an antibacterial.
Diphenhydramine is a histamin (H1) receptor blocker.
Explanation none
level
A3:14
Biotransformation is significant in the pharmacological effects produced by
halothane
methanol
senna
amitriptyline
fieldformat
prednisone
Halothane converted to active materials (responsible for jaundice?).
Methanol converted to formaldehyde and formic acid which have specific toxic effects on retina (go blind) and produce severe acidosis.
Amitriptyline is N-demethylated to nortriptyline which has similar properties and is just as active.
Senna is hydrolysed in the gut, liver and plasma to active sennidin aglycones (purgative).
Prednisone is converted to the active prednisolone.
Explanation none
level
Some sulphonamides
are biotransformed by different routes in different species
may inhibit the biotransformation of other drugs
false
may be inactive as antibacterials until biotransformed
may give rise to metabolic products which damage the kidney
fieldformat
may give rise to metabolic products which damage the liver
Species variation in biotransformation is well established and a hazard in animal models. Sulphaphenazole will inhibit metabolism of phenytion and tolbutamide. Prontosil is a prodrug for sulphanilamide. The acetylated products are less soluble and may crystalise in kidney causing damage.
Explanation none
level
A3:10
The rough endoplasmic reticulum of the liver is concerned directly with the
synthesis of protein for extracellular use
synthesis of cholesterol
metabolism of steroid hormones
level
formation of bile acids
fieldformat
synthesis of glucose-6-phosphatase
false
false
false
The rough endoplasmic reticulum is so called because of the presence of ribosomes, the protein synthesis mechanism of the cell. It has no drug biotransformation function.
Explanation none
A3:11
Possible biotransformation pathways of noradrenaline include:
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
MAO and COMT. Look at the functional groups. Note reuptake in nerves!!
Catechol OH is methylated (catechol-O-methyl-transferase).
Amino group is deaminated (monoamine oxidase).
There is no removable alkyl group in noradrenaline.
Explanation none
A3:12
Possible metabolic pathways for chloral hydrate [C Cl3 CH(OH)2] include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
false
Look at the functional groups. Note this is a prodrug (trichloroethanol). The 2 OH groups on the single carbon are chemically unstable and hydrolysis gives trichloroethanol (active hypnotic). This can be dehalogenated, the alcohol oxidised to an acid and/or be conjugated.
Explanation none
A3:13
Possible biotransformation pathways for isoprenaline include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
MAO & COMT. Look at the functional groups. Not taken up by uptake 1. Catechol OH methylated by catechol-O-methyl-transferase. Alkyl group on nitrogen (isopropyl) removed. Deamination can take place but is very slow. Note importance of uptake2 in the removal of this drug.
Explanation none
A3:13
A3:31
A3:15
Probable biotransformation pathways for dibenzazepines include
hydroxylation
dehalogenation
dealkylation
level
deamination
fieldformat
methylation
false
false
false
Think about the functional groups and the importance of metabolites.
Phenyl ring is hydroxylated and the nitrogen dealkylated.
Deamination is slow because of the two alkyl groups attached to the
nitrogen.
Explanation none
A3:15
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A3:20
A3:28
MCQ:S&B(I)
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1993 Computer Based Learning Unit,
The University of Leeds. v 2.1 9308115
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Documentation
Title: Biotransformations (Hard)
Date: 06-Jan-1992 images added 15-Jul-1993
Contents
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MCQ Help
$Title$
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Title
:PHYSSIZE
Copyright
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Created from c:\ken\pharm\content\a3.idc
23-Nov-1993 (19:09) using Interactive Document Compiler Version 1.36
Biotransformations (Hard)
Department of Pharmacology
The University
Leeds LS2 9JT
England
06-Jan-1992 images added 15-Jul-1993
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LEAVE TOPIC
1993 Computer Based Learning Unit,
The University of Leeds. v 2.2 931123
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