MOA: Exam II

Question 1

Zinc Phosphate / Phosphide / Phosphine Gas

Answer 1

Exact MOA unknown. Direct GI irritation, may inhibit oxidative phosporylation & ATP production. O2 radicals.

Greatest effect on tissues with high O2 demand- brain, heart, liver, kidney, lung.

Question 2

Fluoroacetate / Compound 1080

Answer 2

Competes with citrate in Kreb’s cycle and blocks citrate metabolism. TCA cycle slows and decreased cell respiration/energy production. Citrate binds to Ca2+ and inhibits various enzymes (glutamate, PFK, etc).

Greatest effect on tissues with high energy demand- brain and heart.

Question 3

Metaldehyde

Answer 3

Decreases GABA, norepinephrine, serotonin in brain (decreased GABA therefore decreased inhibition can lead to CNS excitation therefore seizures).

GI irritation, metabolic acidosis, CNS stimulation leads to hyperthermia. Cause of death = respiratory failure. Dogs with acute dz may develop liver failure.

Question 4

2, 4-D / Phenoxyderivatives of Fatty Acids

Answer 4

GI mucosal irritation. Uncouples oxidative phosphyrolation and depresses ribonuclease synthesis. Affects skeletal muscle membrane in dogs.

Question 5

Paraquat / Diquat / Dipyridyl Herbicides

Answer 5

Reduced by NADPH & produces O2 radicals- cell damage and necrosis, esp. lung tissue.

Question 6

Pentachlorophenol (PCP)

Answer 6

Uncouples oxidative phosphorylation, blocks or decreases ATP. O2 demand subsequently increases and exceeds supply therefore overheating, metabolic acidosis, dehydration. Decreased ATP may cause neurotoxic and other effects (weight loss, decreased milk prod., repro problems).

Respiratory mucosa and intact skin irritation.

Question 7

Non-Protein Nitrogen (Urea)

Answer 7

UREA TOX DUE TO AMMONIA.

Ammonia inhibits CAC therefore decrease in ATP, cell respiration, and tissue damage. Increase in [NH3} in blood plus anaerobic glycolysis leads to increased lactate/glucose/BUN/K+/P and systemic acidosis.

Death caused by cardiac failure or resp. failure.

Question 8

Ionophores (monensin / lasalocid / salinomycin)

Answer 8

Disrupts transmembrane electrochemical gradients. Na+ - inonophore influx accompanied by increased intracellular Ca2+. Mitochondria sequester Ca2+, become inhibited, therefore decreased ATP and energy. Cell death due to homeostatic disruption.

Simultaneous catecholamine release results in oxidation products & free radicals causing sarcolemmal membrane damage.

Mainly targets high-energy tissues + mitochondria therefore myocardium, skel. muscles, kidney.

Question 9

Na+ toxicosis / Water deprivation

Answer 9

Normal levels: Blood- 135-145 mEq/L
CSF- 130-140 mEq/L
Abnormal levels: Blood- 150-190 mEq/L
CSF- 145-185.

High Na+ in brain inhibits anaerobic glycolysis, lack of energy to actively pump Na+ out. Osmotic effect draws water in therefore cerebral edema.

Question 10

Inorganic Arsenic

Answer 10

Trivalent / Arsenite binds to 2-SH group of lipoic/thioctic acid, an essential cofactor for ketoacid metabolism, and inhibits it. This causes glycolysis and CAC to slow. Also inhibits oxidative enzymes and inactivates gluathione (GSH)

Pentavalent uncouples oxidative phosphorlyation (NO FEVER!), may interfere with Vit. B1 & B6 metabolism.

Local corrosive effect- capillary endothelial cells most sensitive, followed by intestines, liver, kidney. Targets tissues rich in oxidative enzymes.

Question 11

Organic Arsenic

Answer 11

UNKNOWN.

Peripheral nerve demyelination and axonal damage similar to Vit. B12 deficiency.

Question 12

Copper

Answer 12

Cu2+ accumulation in liver causes degeneration and necrosis. Release/excess Cu2+ in blood causes RBC membrane oxidation therefore weakness and potential hemolytic crisis. Additionally, CU2+ oxidizes hemoglobin to methemoglobin and decreases O2 carrying capacity.

Question 13

Molybdenum

Answer 13

Elevated molybdenum causes copper deficiency by interfering with Cu absorption.

Cu2+ def. involved in hematopoeisis, CT tissue metabolism, myelin formation in young animals, pigmentation and bone formation, and component in essential enzymes (cytochrome oxidase and aromatic amino acid metabolizing enzymes- tyrosinase, dopamine hydroxylase, MAO). Cu-containing proteins (cuprenins) in most aerobic cells have superoxide dismutase activity.

Question 14

Selenium

Answer 14

Dramatic tissue glutathione depletion. Selenium replaces sulfur in amino acids therefore abnormal structure. Decreases ascorbic acid in tissues.

Subacute & Acute: Irritates GI mucosa
Chronic- death may be due to starvation/ thirst resulting from weakness (decreased cellular energy), lameness, blindness.

Question 15

Lead (Pb)

Answer 15

Interferes with biological structure and function- lead can substitute for Ca2+, Mg2+, Zn2+, Fe2+!

Competes with Ca2+ in bone, alters its movement across membranes (eg. BBB)- cerebral endothelial structural change from toxic breakdown can lead to edema. Blood and chronic low-dose exposure inhibits heme synthesis therefore anemia (can also be a result from increased RBC fragility and delayed RBC maturation.)

Target tissues include GI, blood, CNS (may interfere with GABA), alters neurotransmitter release (dopamine, ACh, GABA.)

Question 16

Zinc (Zn)

Answer 16

MOA UNKNOWN

RBCs and kidneys mostly affected.
RBCs undergo hemolysis due to direct membrane/organelle damage. Hapten formation can cause immune-related destruction/direct RBC biochemical mechanism inhibition.
Kidneys affected secondary to anemia, hypoxia, hemoglobinemia, or direct renal tubular epithelial injury.

Question 17

Iron (Fe2+)

Answer 17

Free iron ions very reactive therefore free radical lipid peroxidation, direct cell membrane damage. Primary effect on cardiovascular system, GI, liver leading to shock and death.

Excessive iron can cause myocardial fatty necrosis, post arteriolar dilation, increased capillary permeability, decreased CO. Accumulates in liver causing mitochondrial damage, liver damage, systemic acidosis.

Acute toxicity causes direct corrosion of GI mucosa, vomiting, diarrhea, fluid & electrolyte loss, systemic acidosis, shock.