Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cancer Chemotherapy > Toxicology P1 > Flashcards

Toxicology P1 Flashcards

1
Q

Explain the differences between systemic and local toxic effects

A

Local- occurs at the site of initial contact

Systemic- requires absorption and distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Contrast the basic principles in toxicokinetics and pharmacokinetics

A

The same principles of absorption, distribution, metabolic, and excretion used in pharmacokinetics can be used in toxicokinetics, with the difference being that toxicokinetics takes into account what happens when high doses exceed pharmacokinetic mechanisms.
Thus,
Absorption- may be prolonged
Distribution- apparent volume of distribution may be altered
Metabolism- metabolism may be changed
Excretion- protein binding may be altered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give examples of organ specific toxicities and explain how these specificities are related to physiological or biochemical properties of those organs.

A

CNS is the most sensitive tissue for drug toxicity: Neurons have high metabolic rate - increased oxygen & nutrient requirements; reductions in oxygen, glucose, or oxidative metabolism can cause neuronal damage (cyanide, carbon monoxide)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Discuss the role of bio transformation and detoxification mechanisms in determining the chemical’s toxicity

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Give examples of mechanism based treatments for different types of toxins.

A

Carbon monoxide - oxygen
Carbamate cholinesterase inhibitors - atropine
organophosphate cholinesterase inhibitors - pralidoxime
d-tubocurarine - edrophonium, physostigmine
ethylene glycol, methanol - fomepizole or ethanol
Acetaminophen - N-acetylcysteine
Cyanice- amyl nitrate/sodium nitrite
sodium thiosulfate to form thiocyanate
heavy metals - chelators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain the toxic effects of organophosphate, carbon monoxide, cyanide, methanol, lead, mercury and iron
A. Specific symptoms associated with each of these toxins
B. Discuss physiological defense mechanisms and treatments to diminish their toxicities.

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Discuss important pharmacokinetic concerns and limitations of effectiveness in therapeutic use of chelating agents

A

..

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Discuss the role of pharmacokinetics in the variation in toxicity between individuals exposed to the same chemicals

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe general therapeutic procedures for management of chemical toxicity.

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe principle concerns in supportive treatment of poisoned patients, regardless of toxin.

A

…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Toxic effects dose not equal side effects. Note that like chemotherapeutic agents, toxicity is dose-dependent and the incidence and severity of toxicity is proportional to drug concentration and duration of exposure at the particular tissue site.

Deleterious effects can be grouped into: pharmacological, pathological, genotoxic, idiosyncratic, and allergic

A

Pharmacological- expected symptom based on how the drug interacts with the body (ex. Barbiturates- CNS depression)
Pathological- acetaminophen
Genotoxic- alkylating agents
Idiosyncratic- environmental affect on drug
Allergic- penicillin anaphylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Differentiate acute and chronic toxicity. Note the two properties associated with chronic toxicity:

A

Chronic: 2 properties: usually chemicals are slowly eliminated from the body, allowing accumulation with multiple exposures; effects are irreversible or slowly reversed, even after the chemical has been eliminated

For chronic, note that the effects may not be discernible for a long time and that its due to multiple, long-term exposure to a low level and cumulative chemicals.

Acute can occur in 1-2 days and can have rapid or subacute onset. During rapid onset, interference can occur with critical cellular processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Adverse drug reactions (ADRs) increase exponentially with how many medications?

A

> or equal to 4 medications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the top three most likely causes of ADRs that account for 69% of fatalities?

A
  1. CNS drugs
  2. Cardiovascular drugs
  3. Antineoplastics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Compare/contrast determinants of absorption via inhalation, skin absorption, and ingestion:

A

Inhalation- absorption is dependent on the solubility of the substance in the blood (ie hydrophilic)

Skin- lipid-soluble substances move through the fatty layers of the skin, but hydrophobicity impedes dissolution into blood.

Ingestion: same principles as oral drug administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

T or F: If the volume of distribution is > 1 L/kg, it is effective to enhance elimination by hemodialysis?

A

False; drugs that are highly tissue bound will have a higher Vd. However, since the drug is more tissue bound, less is found in the vascular system, and elimination based on hemodialysis would be futile. Removal of the drug from the vascular system will simply allow for it to re-equilibrate with drug from the stored tissues.

Thus, in terms of toxicokinetics, it is difficult to determine the volume of distribution, as you do not know the dose, and you have limited time to determine the plasma concentration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Note, the total amount of toxin cleared per unit time depends on plasma concentration. Recall from pharmacokinetics that for first-order elimination, clearance is exponentially proportional to concentration, the higher the conc. The greater the clearance. However, with toxic concentrations of a drug, clearance mechanisms may be oversaturated, and thus, clearance of the drug will follow zero-order kinetics. In this situation, clearance is not dependent on concentration, but will be linear.

A

See front.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Why is atropine administration for an organophosphate overdose only partially effective?

A

Atropine only blocks muscarinic receptors, but not nicotinic receptors. Thus, activity is still present at Nm (NMJ nicotinic receptors) or at Nn (nicotinic receptors on nerve terminals). Thus, atropine can reverse respiratory depression, bronchoconstriction, tracheaobronchial secretions; however, it does not reverse neuromuscular blockade.

19
Q

AChE much more resistant to reactivation after aging (alkyl groups cleaved from phosphate)

A

Once the alkyl group is cleaved from phosphate, aging occurs and AChE is much more resistant to reactivation.

20
Q

What is a limitation of pralidoxime?

A

Although it can be used to reverse AChE inhibition, it cannot cross into the CNS and thus is ineffective for CNS toxicity.

21
Q

What is an important use for N-acetylcysteine?

A

Acetaminophen can become toxic if the glutathione-conjugation system is saturated. N-acetylcysteine can readily enter hepatocytes and converts to glutathione to bind reactive acetaminophen.

22
Q

Methemoglobin is important for trapping cyanide, causing it to bind to methemoglobin over hemoglobin. What two drugs are used in order to convert hemoglobin to methemoglobin?

A

Amyl nitrite and sodium nitrite; methemoglobin iron serves as a large pool of ferric iron.

23
Q

Polymorphic distribution

A

A trait that has differential expression in >1% of the population.

24
Q

What two cells found in the lungs is responsible for biotransformation of inhaled particulate due to their expression of CYP450?

A

Clara cells and Alveolar Type II

25
Q

In the lungs, parquot can form super oxide ions and cause epithelial membrane damage. What can result from this superoxide damage?

A

lung edema and fibrosis.

26
Q

Tetracyclines, sulfonamides, chlorpromazine, and nalidixic acid acts as photosensitizes. What is their mechanism of action?

A

These compounds will readily absorb UV radiation and cause damage and recruitment of inflammatory cells.

27
Q

T or F: While the skin is a protective barrier, most chemicals will penetrate to some extent and enter systemic circulation?

A

True

28
Q

Both inhaled toxins and ingested toxins can reach the liver and cause toxicity. By what routes will these toxins reach the liver?

A

Inhaled toxins reach the liver via systemic circulation (hepatic arteries)
Ingested toxins reach the liver via the portal vein, from intestinal absorption.

Note that the liver has repeated exposure through enterohepatic recirculation.

29
Q

95% of acetaminophen is conjugated by either glucuronidation or sulfation. The remaining 5% is conjugated by what enzyme, producing a toxic compound.

A

CYP2E1/CYP3A4- same enzyme used in ethanol metabolism

30
Q

What compound is produced by detoxification of the reactive intermediate produced by enzymes CYP2E1 and CYP3A4 on acetaminophen?

A

Mercapturic acid is produced and excreted. However, if reactant exceeds GSH capacity, the electrophile reacts with nucleophiles (DNA, proteins). this will ultimately lead to liver cell death.

31
Q

Where is the site in the kidney where most damage occurs? Why?

A

Proximal tubule- biotransformation occurs here (ex. CCl4, CHCl3), toxins can be bound by metallothioneins, and can also accumulate in the proximal tubules)

32
Q

Explain why reductions in oxygen, glucose, or oxidative metabolism can have damaging effects on the CNS?

A

Neurons have high metabolic rates with increased oxygen & nutrient requirements. Examples of drugs that can impose neuronal toxicity are cyanide and carbon monoxide. Both will decrease oxygen levels.

Also note that the axon is particularly susceptible to neuronal damage.

33
Q

What is the importance of benzene’s activation by myeloperoxidase?

A

Myeloperoxidase, a peroxisome found mainly in neutrophils but also in monocytes, activates benzene, which can ultimately lead to aplastic anemia.

34
Q

Differentiate Type I, II, III, and IV hypersensitivity reactions

A

Type 1 = anaphylaxis (penicilin)- mediated by IgE bound to mast cells and basophils which will release immune mediators

Type II= cytolytic (penicilin, sulfonamides, quinine) - IgG or IgM reactions that ultimately cause the destruction of cells by stimulation of complement-mediated cytotoxic mechanisms.

Type III = IgG mediated reaction to antibody-antigen complexes

Type IV = Activated T-helper cells, causing proliferation and release of cytokines

35
Q

Will atropine administration reverse neuromuscular blockade?

A

No, only muscarinic blockade. Neuromuscular/nicotinic stimulation presents with HTN, tachycardia, muscle fasciculation and mental confusion

36
Q

Pralidoxime/atropine administration have aging has occurred with binding of a AChE inhibitor will prove futile for reversing the inhibition of the cholinesterase. What is the reaction that causes aging?

A

Loss of an alkyl group from the phosphorylated enzyme results in its irreversible binding to the cholinesterase.

Note: It takes up to 20 days to reactivate AChE stores

37
Q

Give examples of neuromuscular blockade to Ach signaling to nicotinic and muscarinic receptors.

A

Nicotinic- d-tubocurarine

Muscarinic- atropine (succinylcholine- depolarizing)

38
Q

Reversal of d-tubocurarine is successful by what two drugs?

A

AChE inhibitors: edrophonium and physostigmine (can be used prophylactically)

39
Q

Explain cyanide toxicity. What drugs can be used to reverse toxicity?

A

Cyanide binds ferric iron (Fe3+, oxidized) and prevents it from reducing to ferrous iron (Fe2+). Ferrous iron is necessary for cytochrome oxidase in the electron transport chain. Thus causing the cell to rely on anaerobic respiration which increases lactic acid, leading to hypoxia and acidosis.

40
Q

How is cyanide toxicity reversed?

A

Sodium nitrate and amyl nitrate is given to form methemoglobin (Fe3+), which can bind and trap cyanide.

cyanmetHb can be further metabolized to thiocyanate by sulfotransferases and the addition of the substrate, thiosulfate

41
Q

Ultimately, what is the excreted product for cyanide reversal?

A

Thiocyanate

42
Q

Why can alcohol be given to reverse toxicity caused by ethylene glycol and methanol?

A

Alcohol competes with the enzyme alcohol dehydrogenase (the same enzyme responsible for converting ethylene glycol and methanol into glycolic and formic acid). Ethanol has 100x greater affinity for ADH and EtOH oxidation is 7x faster.

43
Q

Accumulation of glycolic and formic acid can result in what?

A
  • ocular damage
  • metabolic acidosis
  • respiratory depression
    COMA & DEATH
44
Q

What drug is useful in blocking alcohol dehydrogenase in an effort to reduce formation of glycolic and formic acid?

A

Fomepizole

Cancer Chemotherapy (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions