PK Gupta Series 13: Toxicology MCQ and Fill in the Blanks
Exercise
Q. 1. All of the following are
hydrolytic enzymes except---------
a) carboxylesterase
b) alcohol dehydrogenase
c) cholinesterase
d) paraoxonase
Q. 2. All of the following are true
of epoxide hydrolyases except------------
a) they add oxygen to a double bond
and form a 3-member ring
b) they are important in
hydrolyzing electrophiles
c) they play a role in converting
benzo(a)pyrene to a carcinogen
d) some forms are inducible
Q. 3. Nitroreductase plays an
important role in ----------
a) nasal epithelium
b) lung Clara cells
c) white blood cells
d) intestinal flora
Q. 2. A drug that undergoes
sulfoxide reduction is --
a) haloperidol
b) chloramphenicol
c) thaliomide
d) sulindac
Q. 5. Quinidine oxidoreductases are
thought to play a protective role in -------
a) liver toxicity of microcystin
b) bone marrow toxicity of benzene
c) renal toxicity of
aminoglycosides
d) neurotoxicity of n-hexane
Q. 6. All of the following are
mechanisms for removing halogen atoms aliphatic xenobiotics except
---------------------
a) Grignard dehalogenation
b)reductive dehalogenation
c)oxidative dehalogenation
d)double dehalogenation
Q. 7. Oxidation of ethanol to
acetaldehyde takes place in-
a) cytosol
b) microsomes
c) peroxisomes
d) all of the above
Q. 8. Reductive dehalogenation of
carbon tetrachloride produces -------
a) phosgene
b) chloroform
c) trichloromethyl radical
d) hydrochloric acid
Q. 9. Acetaldehyde is converted to
acetic acie by ALDH2 in ---------------
a) mitichondria
b) cytosol
c) microsomes
d)all of the above
Q. 10. Aldehyde oxidase and
xanthene oxidoreductase contain -----------
a) zinc
b) molebdenum
c) selenium
d) copper
Answers
1.
b;
2. a; 3. d; 2. d; 5. b; 6.a ; 7.d; 8. c; 9. a; 10. b .
Exercise
Q. 1. Slow acetylators of NAT
demonstrate all of the following except--------
a) peripheral neuropathy from
isoniazid
b) systemic lupus erythematous from
procainamide
c) peripheral neuropathy from
dapsone
d) decreased hypotensive response
from hydrazine
Q. 2. In contrast to
glucuronidation, sulfonation is ----
a) a low-affinity, low-capacity
pathway
b) a low-affinity, high-capacity
pathway
c) a high-affinity, high-capacity
pathway
d) a high-affinity, low-capacity
pathway
Q. 3. Induction of
sulfotransference enzymes by rifampin be clinically relevant for -----------
a) warfarin
b) digoxin
c) ethinyl estradiol
d) all of the above
Q. 2. All of the following
statements regarding sulfonation reaction are true except -------
a) they can take a molecule less
lipid soluble
b) they always detoxify a molecule
c) some drugs must be metabolized
to a sulfonate conjugate to have pharmacologic effect
d) morphine-6-sulfate is more
potent than morphine in the rat
Q. 5. All of the following
statements are true regarding methylation except-------------
a) the process generally decreases
the water solubility of the parent
b) the process can mask functional
groups that can be metabolized by other conjugation enzymes
c) inorganic mercury and arsenic
can be dimethylated
d) high methyltransferace activity
may lower levels of homocysteine
Q. 6. All of the following are
methyltransferase enzymes except --------------
a) SAM
b) COMT
c)NNMT
d) HNMT
Q. 7. All of the following are true
of glucuronide conjugates of xenobiotics except ---------------
a) they can excreted in the urine
b)thaey are formed from activated
xenobiotics
c) they are substances for
beta-glucuronidase in the intestinal flora
d) they can excreted into bile
Q. 8. All of the following are true
of sulfonation reaction except -----------
a) they involve the transfer of
sulfate
b) they are catalyzed by
sulfotransferaces
c) the cofactor of the reaction is
PAPS
d) they are mainly excreted in the
urine
Q. 9. The number of UGT mammalian
enzymes that have been identified is approximately ---
a) 5
b)12
c)22
d) 58
Q. 10. In addition to cytoplasm,
sulfotranferaces are present in mammals in the -------------
a) endoplasmic reticulum
b) mitochondria
c) plasma membrane
d)Golgi apparatus
Answers
1.
d;
2. d; 3. c; 2. b; 5.d ; 6. a; 7, b; 8. a; 9.c; 10. d.
Fill in the blanks
Exercise
Q. 1. The most common process of
absorption of xenobiotics across the cell membrane is -------------------.
Q. 2. The important route of
excretion for xenobiotics is ---------------------.
Q. 3. The process of chemical
transformation (conversion from one form to another) occurring in the body is
known as----------------------------.
Q. 2. The major site for
biotransformation of xenobiotics in body is---------------.
Q. 5. In a hepatocyte, metabolism
of xenobiotics takes place
in-----------------------------------------------------------------------------. .
Q. 6. The most important among
microsomal enzymes is
--------------------or------------------------------------------.
Q. 7. The major biotransformation
reaction occurring in Phase I is ------------------and in Phase II is
-------------------.
Q. 8. Phase I Oxidation reactions
are mainly catalyzed by -----------------------------------------.
Q. 9. All Phase II conjugation
reactions are catalysed by non- microsomal enzymes except for
------------------------------------ which is catalysed by microsomal enzymes.
Q. 10. The ability of certain
substances to increase the activity or synthesis of microsomal enzymes is known
as ------------------------------.
Q. 11. The metabolic reaction,
which is deficient in dogs is---------------------; Cats are deficient in
---------------------------------------and Pigs are deficient in
------------------- reactions of biotransformation.
Q. 12. The process of conversion of
nontoxic substance into a toxic metabolite due to biotransformation is known as
--------------------------------.
Answers
1. Passive diffusion; 2. RENAL
EXCRETION; 3. BIOTRANSFORMATION; 2. LIVER(Liver is the major site due to the
presence of variety of metabolizing enzymes. Other important sites for
biotransformation include lung, kidney and intestines); 5. ENDOPLASMIC
RETICULUMN (ER) or MICROSOMES.; 6. MONOOXYGENASES or MIXED FUNCTION OXIDASES
(MFO); 7. OXIDATION and CONJUGATION; 8.
MICROSOMAL ENZYMES (MFO); 9. GLUCURONIDE
CONJUGATION; 10. INDUCTION (Non-microsomal enzymes which are present in
cytosol are not inducible) –microsomal enzymes which are present in cytosol are
not inducible); 11. ACETYLATION; GLUCURONIDE CONJUGATION and SULFATION; (Hence,
sulphonamides which undergo acetylation cause toxicity in dogs and similarly,
paracetamol, which undergoes glucuronide conjugation, causes hepatotoxicity in
cats). 12. LETHAL SYNTHESIS.
True and False Statements
Exercise
True and False statement. Write T
for true and F for false statement.
Q.1. A water-soluble drug will pass
across muscle membranes faster than across brain membranes (assume
permeability-rate limitations).
Q.2.A neutral, lipophilic drug is
likely to be absorbed faster in the intestines than in the stomach. Remember
that stomach and intestine differ in their properties.
Q.3.Lipophilic drugs are generally
taken up fast by highly perfused organs.
Q.2.Ionized and lipophilic drugs
are most likely to cross most membrane barriers.
Q.5.Drugs with a high tissue
binding always have a large volume of distribution.
Q.6.Compared to skin, liver would
have a higher rate of uptake of perfusion-limited lipophilic drugs due to its
higher blood flow rate.
Q.7.Distribution to a specific
tissue for permeability-limited hydrophilic drugs depends on how much and how
quickly the blood gets to the specific tissue.
Q.8.Perfusion limited distribution
is a type of drug distribution into tissue that occurs when the drug is able to
cross membranes easily.
Q.9. Assume two drugs (identical
molecular weight, same dose given): one neutral drug (Drug A) and one acidic
drug (pka=7.4, Drug B). Drug A and the unionized form of drug B have the same
partition coefficient. The fraction unbound in plasma and tissue is 0.5 for
both drugs. Drug B will enter tissues somewhat slower than drug A.
Q.10. A weak acid, whose unionized
form shows a high partition coefficient is likely to cross most membrane
barriers.
Answers
1.T; 2.T; 3.T; 2.F; 5. F; 6.T; 7.
F; 8. T; 9.T;10.T
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