NUSCTX 110 MIDTERM 1 EXAM
QUESTIONS WITH COMPLETE
ANSWERS
Albumin - Answer-the most abundant protein in plasma- can bind to a very large
number of different compounds—(e.g. bilirubin, Ca2+, Cu2+, Zn2+, vitamin C, fatty
acids, digitonin, penicillin, sulfonamides, histamine, barbiturates, thyroxine, etc.)
Liver and Kidney as Storage Depots - Answer-have the highest capacity for binding
chemicals. 1. Ligandin: this cytoplasmic protein in the liver is a high-affinity binding
protein for many organic acids—can bind bilirubin, azodye carcinogens, steroids,
etc.2. Metallothionein: found in the kidney and liver and has high affinity for cadmium
and zinc--in the liver, metallothionein binds Lead (Pb) and concentrates it to 50-fold
more than plasma.
Fat as a Storage Depot - Answer-Many highly lipophilic toxicants are distributed and
concentrated in fat (e.g. dioxin, DDT, polychlorinated biphenyls)-
The LD50 of a fat-stored compound will be higher in an obese subject.
-However, a quick weight-loss can result in large release of toxicant and toxic effect.
Bone as Storage Depot - Answer-1. Compounds such as fluoride, lead, and
strontium may be incorporated and stored in bone matrix.
2. 90% of lead in the body is eventually found in the skeleton.
3. The mechanism of storage is through exchange of bone components for the
toxicant (e.g. Pb2+ and Sr2+ may substitute for Ca2+ in the hydroxyapatite lattice
matrix).
Effects of Storage on Toxicity - Answer-1.Reduces toxicity of some substances by
taking toxic substances out of the sites of action.
2.Increases toxicity if: a)toxicity at storage site, b) displacement of one substance by
another (e.g. bilirubin), loss of storage site.
3.Can produce chronic toxicity from prolonged exposure.
Blood-Brain Barrier - Answer-The blood-brain barrier serves to restrict access to
many toxicants. It is not an absolute barrier. It is a site that is less permeable to more
hydrophilic substances than are most other areas of the body.
Capillary endothelial cells - Answer-of the CNS are tightly joined, leaving few or no
pores between cells.
multi-drug-resistant - Answer-
- Answer-Brain capillary endothelial cells contain an ATP-dependent transporter, the
multi-drug-resistant (mdr) protein that transports some chemicals back into the
blood.
, Capillaries in the CNS - Answer-Capillaries in the CNS are surrounded by glial cells
(astrocytes) to further restrict access.
protein concentration in the interstitial fluid - Answer-The protein concentration in the
interstitial fluid of the CNS is much lower than in other body fluids.
For water-soluble molecules, the tighter junctions of the capillary endothelium -
Answer-•For water-soluble molecules, the tighter junctions of the capillary
endothelium and the lipid membranes of the glial cells represent the major barrier.
lipid membranes to be crossed - Answer-•Many lipid soluble compounds are
restricted due to the many lipid membranes to be crossed (capillary and glial cell
membranes) and low protein content.
blood-brain barrier is more effective - Answer-•The blood-brain barrier is more
effective against water soluble substances.
Methyl Mercury Transport - Answer-Methylmercury combines with cysteine, forming
a structure similar to methionine, which is transported across the blood brain barrier
through the methionine transporter in endothelial cells
Once in the brain, methyl mercuric cysteine can react with reactive cysteines on
proteins and cause neurotoxicity
ATP-binding cassette - Answer-The ATP-binding cassette (ABC) transporters form a
large family of membrane proteins that transport a variety of compounds through the
membrane against a concentration gradient at the cost of ATP hydrolysis.
Substrates include lipids, bile acids, xenobiotics, and peptides for antigen
presentation. As they transport exogenous and endogenous compounds, they
reduce the body load of toxicants.
One by-product of such protective function is that they also eliminate various useful
drugs from the body, causing drug resistance. Many types of cancer cells can up-
regulate MDR (multidrug resistant).
1.In general, if you're exposed to a toxicant that causes toxicity through systemic
absorption, which routes of administration would cause the most toxicity in rank
order? - Answer-a)Dermal (most toxic)>IP>inhalation>IV (least toxic)
b)IV (most toxic)>inhalation>dermal>IP>oral (least toxic)
c)Inhalation (most toxic)>dermal>oral>IV (least toxic)
d)Oral (most toxic)>IV>inhalation>IP (least toxic)
3.Which routes of administration could go through first pass metabolism? - Answer-
a)IV
b)Dermal
c)Intramuscular
d)oral
QUESTIONS WITH COMPLETE
ANSWERS
Albumin - Answer-the most abundant protein in plasma- can bind to a very large
number of different compounds—(e.g. bilirubin, Ca2+, Cu2+, Zn2+, vitamin C, fatty
acids, digitonin, penicillin, sulfonamides, histamine, barbiturates, thyroxine, etc.)
Liver and Kidney as Storage Depots - Answer-have the highest capacity for binding
chemicals. 1. Ligandin: this cytoplasmic protein in the liver is a high-affinity binding
protein for many organic acids—can bind bilirubin, azodye carcinogens, steroids,
etc.2. Metallothionein: found in the kidney and liver and has high affinity for cadmium
and zinc--in the liver, metallothionein binds Lead (Pb) and concentrates it to 50-fold
more than plasma.
Fat as a Storage Depot - Answer-Many highly lipophilic toxicants are distributed and
concentrated in fat (e.g. dioxin, DDT, polychlorinated biphenyls)-
The LD50 of a fat-stored compound will be higher in an obese subject.
-However, a quick weight-loss can result in large release of toxicant and toxic effect.
Bone as Storage Depot - Answer-1. Compounds such as fluoride, lead, and
strontium may be incorporated and stored in bone matrix.
2. 90% of lead in the body is eventually found in the skeleton.
3. The mechanism of storage is through exchange of bone components for the
toxicant (e.g. Pb2+ and Sr2+ may substitute for Ca2+ in the hydroxyapatite lattice
matrix).
Effects of Storage on Toxicity - Answer-1.Reduces toxicity of some substances by
taking toxic substances out of the sites of action.
2.Increases toxicity if: a)toxicity at storage site, b) displacement of one substance by
another (e.g. bilirubin), loss of storage site.
3.Can produce chronic toxicity from prolonged exposure.
Blood-Brain Barrier - Answer-The blood-brain barrier serves to restrict access to
many toxicants. It is not an absolute barrier. It is a site that is less permeable to more
hydrophilic substances than are most other areas of the body.
Capillary endothelial cells - Answer-of the CNS are tightly joined, leaving few or no
pores between cells.
multi-drug-resistant - Answer-
- Answer-Brain capillary endothelial cells contain an ATP-dependent transporter, the
multi-drug-resistant (mdr) protein that transports some chemicals back into the
blood.
, Capillaries in the CNS - Answer-Capillaries in the CNS are surrounded by glial cells
(astrocytes) to further restrict access.
protein concentration in the interstitial fluid - Answer-The protein concentration in the
interstitial fluid of the CNS is much lower than in other body fluids.
For water-soluble molecules, the tighter junctions of the capillary endothelium -
Answer-•For water-soluble molecules, the tighter junctions of the capillary
endothelium and the lipid membranes of the glial cells represent the major barrier.
lipid membranes to be crossed - Answer-•Many lipid soluble compounds are
restricted due to the many lipid membranes to be crossed (capillary and glial cell
membranes) and low protein content.
blood-brain barrier is more effective - Answer-•The blood-brain barrier is more
effective against water soluble substances.
Methyl Mercury Transport - Answer-Methylmercury combines with cysteine, forming
a structure similar to methionine, which is transported across the blood brain barrier
through the methionine transporter in endothelial cells
Once in the brain, methyl mercuric cysteine can react with reactive cysteines on
proteins and cause neurotoxicity
ATP-binding cassette - Answer-The ATP-binding cassette (ABC) transporters form a
large family of membrane proteins that transport a variety of compounds through the
membrane against a concentration gradient at the cost of ATP hydrolysis.
Substrates include lipids, bile acids, xenobiotics, and peptides for antigen
presentation. As they transport exogenous and endogenous compounds, they
reduce the body load of toxicants.
One by-product of such protective function is that they also eliminate various useful
drugs from the body, causing drug resistance. Many types of cancer cells can up-
regulate MDR (multidrug resistant).
1.In general, if you're exposed to a toxicant that causes toxicity through systemic
absorption, which routes of administration would cause the most toxicity in rank
order? - Answer-a)Dermal (most toxic)>IP>inhalation>IV (least toxic)
b)IV (most toxic)>inhalation>dermal>IP>oral (least toxic)
c)Inhalation (most toxic)>dermal>oral>IV (least toxic)
d)Oral (most toxic)>IV>inhalation>IP (least toxic)
3.Which routes of administration could go through first pass metabolism? - Answer-
a)IV
b)Dermal
c)Intramuscular
d)oral
