Mechanisms of Toxicity

Question 1

Sustain elevation of intracellular calcium (Ca^2+) is harmful for all of these reasons except:

a) depletion of energy reserves by inhibiting the ATPase used in oxidative phosphorylation,
b) dysfunction of microfilaments,
c) change of cell membrane polarization,
d) activation of hydrolytic enzymes,

Answer 1

c) change of cell membrane polarization,

should be generation of ROS and RNS in cells

Question 2

Chemical carcinogenesis is dependent all of the following except:

a) failure of DNA repair
b) nuclear receptor activation
c) failure of apoptosis
d) failure to terminate cell proliferation

Answer 2

b) nuclear receptor activation

Question 3

Which of the following features of chemical distribution favor accumulation of a toxicant in the liver or kidneys?

a) Reversible intracellular binding
b) Specialized transport across the plasma membrane
c) Accumulation in cell organelles
d) Porosity of the capillary endothelium

Answer 3

d) Porosity of the capillary endothelium

Endothelial cells in the hepatic sinusoids and the renal peritubular capillaries have large fenestrae that permit the passage of even protein-bound xenobiotics.

Question 4

Which feature of distribution is likely to employ membrane recycling or endocytosis?

a) Specialized transport across the plasma membrane
b) Porosity of the capillary endothelium
c) Reversible intracellular binding
d) Accumulation in cell organelles

Answer 4

a) Specialized transport across the plasma membrane

Specialized ion channels, membrane transporters or bulk transport by receptor-mediated phagocytosis can deliver toxicants tot he intracellular space. Sodium, potassium-ATPase, voltage-gated calcium channels, carrier mediate uptake, endocytosis, and membrane recycle all contribute to this mode of distribution.

Question 5

Warfarin is highly bound to plasma with little affinity for tissue distribution. Ethanol tends to distribute into the body water. Propranolol distributes into peripheral tissues. Chloroquine has high tissue uptake and is trapped in lysosomes. Match each of these to a likely Vd.

a) 4.3
b) 0.1
c) 100
d) 0.5

Answer 5

a) 4.3 - Propranolol
b) 0.1 - Warfarin
c) 100 - Chloroquine
d) 0.5 - ethanol

Volume of distribution is the volume in which the drug would need to be uniformly dissolved in order to produce the observed blood concentration. PFOA has a Vd of 0.127 L/kg.

Question 6

The Fenton reaction:

a) donates an electron from HOOH to Fe (or other similar metals) to generate a reactive metal species
b) coverts HOOH to HO* and -OH via a transition metal like Fe
c) conversion of HO* and -OH to HOOH via a transition metal, like Fe, resulting in cellular damage
d) Converts H2O to HO* and -OH via a transition metal like Fe

Answer 6

b) coverts HOOH to HO* and -OH via a transition metal like Fe

The Fenton reaction involves the formation of •OH radicals from hydrogen peroxide by an electron transfer between a redox active metal (usually ferrous iron) and H2O2

Question 7

Which of the following is an acetylcholine nicotinic receptor agonist and its effect?

a) Pb, muscle fibrillation
b) Pb, muscle paralysis
c) nicotine, muscle fibrillation
d) nicotine, muscle paralysis

Answer 7

c) nicotine, muscle fibrillation

Acetylcholine agonism activates the parasympathetic nervous system