pt 3: target organ toxicity

Question 1

The fact that hepatic lesions are often centrilobular has been attributed to the HIGHER concentration of (1)——- there. In addition, the relatively LOWER concentration of (2)——– there, compared to that in other parts of the liver

Answer 1

(1) cytochrome P-450

(2) glutathione

Question 2

carbon tetrachloride leads to which toxic subcellular effects on organelles in liver cells?

Answer 2

• enzyme leakage from plasma membrane
  and
  -mitochondria swelling

Question 3

enzyme leakage from plasma membrane of liver cells is caused by which toxicants

Answer 3

acetaminophen, carbon tetrachloride, phalloidin

Question 4

nucleus neoplasia of liver cells is caused by which toxicants

Answer 4

aflatoxin, tannic acid,…

Question 5

mitochondria swelling of liver cells is caused by which toxicants

Answer 5

carbon tetrachloride, cycasin, phosphorus.

Question 6

-1- what agents produce acute hepatic lesions?

-2- what agents produce both acute and chronic lesions?

Answer 6

-1- ethionine, phosphorus, or tetracycline

-2- Ethanol and methotrexate

Question 7

what is the most common mechanism of lipid accumulation in the liver

Answer 7

the impairment of the release of hepatic triglyceride to the plasma.

Question 8

carbon tetrachloride exerts toxicity via its metabolite trichloromethyl through several MOAs leading to liver necrosis, which include:

Answer 8

-lipid peroxidation
-disturbances of Ca2+ homeostasis
-depletion of adenosine triphosphate (ATP),
-shifts of the Na+ and K+ balance between hepatocytes and blood,
-depletion of glutathione,
-damage to cytochrome P-450, and
-loss of NAD and NADP

Question 9

Reduction of biliary excretory activity of the canalicular membrane appears to be the predominant mechanism for ——-

Answer 9

cholestasis

Question 10

——- seem to impair the permeability of the biliary tract, thus reducing bile salt–independent bile flow

Answer 10

Ethinyl estradiol and chlorpromazine

Question 11

The pathogenesis of cirrhosis in a majority of cases seems to originate from single-cell —– associated with a deficiency in the repair mechanism.

Answer 11

necrosis
-This condition then leads to fibroblastic activity and scar formation

Question 12

The most important cause of human cirrhosis is chronic ingestion of alcoholic beverages.
—- may damage mitochondria and increase local production of reactive oxygen species. These may lead to steatosis, necrosis, and cirrhosis

Answer 12

Ethanol

Question 13

what are characteristics of drugs that cause viral-like hepatitis

Answer 13

1. such liver injuries are not demonstrable in animals
2. the effects in humans do not seem to be related to the dose
3. the latent period varies greatly
4. the toxicity is manifest in only a few susceptible individuals
5. the histologic picture is more variable
6. the patients usually show other signs of hypersensitivity and sometimes respond to a challenge dose
7. fever, rash, and eosinophilia are present in many cases.

Question 14

—– induces hepatocarcinogenesis via a nongenotoxic mechanism only in the mouse and not in the rat

Answer 14

Dieldrin

Question 15

—— in addition to producing hepatotoxicity also induces hepatocellular adenoma and carcinoma

Answer 15

Fumonisin B

Question 16

steatosis, necrosis, and cirrhosis can result from exposure to —–

Answer 16

• CCl4 (and related chemicals such as chloroform),
• aflatoxins, and
• phosphorus.

Question 17

——– was shown to produce liver cell death by depletion of glutathione and an oxidative phase characterized by mitochondrial permeability transition and protein nitration

Answer 17

chloroform

Question 18

The serum level of alanine aminotransferase (ALT) is increased in reliable correlation with the severity of hepatic ——-. It is therefore the choice test in this liver injury.

Answer 18

necrosis

-OCT and SDH are more sensitive but less specific, so they’re used in addition to ALT

Question 19

Measurements of barbiturate-induced sleeping time and the duration of zoxazolamine-induced paralysis have been used as indications of ——- effects

Answer 19

hepatic

Question 20

what tests are used to detect liver function

Answer 20

ALT / OCT / SDH / bilirubin LS / BSP excretion MS / prolongation of prothrombin time (after vitamin K excretion) / drugs like BARBs-induced sleeping time and zoxazolamine-induced paralysis.

Question 21

acetaminophen, aflatoxin, allyl alcohol, ethanol, ethionine, fumonisin B
the following are toxic to what type of injury

Answer 21

necrosis and fatty liver

Question 22

p-aminosalicylic acid, amitriptyline, carbamazapine
M
the following are toxicants of what type of injury

Answer 22

cholestasis (drug induced)

Question 22

imipramine
cholchicine
halothene

the following are toxicants of what type of injury

Answer 22

viral-like hepatitis (drug induced)

Question 23

-acetylaminofluorene
-aflatoxin B1
-Cycasin

the following are toxicants of what type of injury

Answer 23

carconogenesis in experimental animals

Question 24

what are the most sensitive and consistent indicators of nephrotoxicity

Answer 24

In vitro accumulation of organic ions, urinary concentrating ability, and kidney weight

Question 25

what is the most sensitive indicator of the nephrotoxicity of a platinum complex

Answer 25

urine osmolarity

Question 26

what halogenated hydrocarbons are nephrotoxicants, and what is the site of toxicity

Answer 26

bromobenzene, chloroform, carbon tetrachloride site: proximal tubule

Question 27

what heavy metals are nephrotoxicants, and what is the site of toxicity

Answer 27

- cadmium and chromium are toxic at the proximal tubules - Gold is toxic at the Glomeruli

Question 28

what antibiotics are nephrotoxicants, and what is the site of toxicity

Answer 28

-Aminoglycoside: at glomeruli and proximal tubules -Amphotericin B: glomeruli and blood vessels and distal tubules - Cephaloridine: proximal tubules

Question 29

what analgesics are nephrotoxicants, and what is the site of toxicity

Answer 29

-Acetaminophen: various parts of the nephron and blood vessels -Methoxyflurane: various parts of the nephron

Question 30

what patient groups are more susceptible to chemical-induced nephrotoxicity.

Answer 30

geriatric males

Question 31

what are MOAs of NEPHROTOXICANTS

Answer 31

- interaction with receptors, - inhibition of oxidative phosphorylation -disturbance of Ca2+ homeostasis -adverse effects in plasma and subcellular membranes

Question 32

------ induce a nephropathy with functionally a decease in renal volume, but histologically there is thickening of the basement membrane of the LOOP OF HENLE, isolated necrosis of interstitial and papillary tubular cells followed by fibrosis and cortical interstitial nephritis

Answer 32

Analgesics

Question 33

which antibiotic is not secreted from the proximal tubules but is accumulated in these cells, thereby producing damage.

Answer 33

cephaloridine

Question 34

The antibiotic -------- can increase the permeability of the glomerulus to proteins such as ALBUMIN. This has been attributed to an alteration in the electrical charge of glomerular basement membrane

Answer 34

puromycin

Question 35

Certain toxicants, for example, ------, may induce membranous glomerulonephritis by the deposition of ANTIGEN-ANTIBODY conjugates in the glomerular basement membrane.

Answer 35

gold, mercury, and penicillamine

Question 36

------ produces acute thrombotic microangiopathy and chronic nephropathy with interstitial fibrosis

Answer 36

Cyclosporin

Question 37

-------, produce chronic renal failure, with adverse effects located predominantly in the medulla, that is, loop of Henle, vasa recta, interstitial cells, and collecting tubules.

Answer 37

Analgesic mixtures containing aspirin and phenacetin, a derivative of acetaminophen - due to vasoconstriction of the vasa recta

Question 38

------ were reported to produce inflammatory interstitial nephritis in humans.

Answer 38

Penicillins and sulfonamides