Buxton: Toxicology Flashcards by Megan Foggia

5 things that the dose is dependent on

the environmental concentration
properties of the toxin
pathway of exposure
duration of exposure
frequency of exposure

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What’s the ED50?

the median effective dose; the dose at which 50 percent of the population or sample manifests a given effect

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What’s the TD50?

the median toxic dose; the dose at which 50 percent of the population or sample manifests a toxic effect

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What’s the LD50?

dose which kills 50% of the subjects

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What’s the difference between NOEL and MABEL?

NOEL is the dose at which there is no observable effect, while MABEL is the dose at which there is a minimal anticipated biological effect

**MABEL is probably a better measure

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The (higher/lower) the therapeutic index, the better the drug.

higher

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Drugs acting on the same (blank) often have the same therapeutic index

receptor or enzyme

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Give an example of a drug with both therapeutic and toxic effects. What happens when the dose is too low? Too high?

Vit A; too low: blindness, dry skin, increased infection; too high: anorexia, anemia, nose bleeds, muscle and joint pain

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T/F: LD50 can range from 0.0001 mg/kg to 10,000 mg/kg

True

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Rank the typical effectiveness of different routes of drug exposure

iv > inhale > IP > IM > ingested > topical

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Drug absorption through epidermis (stratum corneum), then dermis is called (blank)

percutaneous

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Some drugs that are very lipophylic, like DDT, will store in (blank). Rapid mobilization of the (blank) can rapidly increase the blood concentration.

fat

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Some drugs will be stored in (blank), like fluoride, lead, and strontium

bone

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Some drugs will become bound to (blank), in which case they will not be available for adverse effects

plasma proteins

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What are some ways in which drugs interfere with proteins, lipids, RNA, and DNA?

receptor-ligand binding
membrane function
cellular energy production
membrane ion channels
perturb homeostasis

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Think of 4 ways in which drugs can be excreted

urinary
exhalation
biliary/fecal excretion
milk, sweat, saliva

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What is the primary objective of metabolism?

to make chemical agents more water soluble and easier to excrete

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4 ways to increase metabolism and make a drug easier to excrete

decrease its lipid solubility
decrease amount at target
increase ionization
increase excretion rate

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(blank) is frequently the single most important determinant of the duration and intensity of the pharmacological response to a chemical

metabolism

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(blank) is a parasympathomimetic; acetylcholinesterase inhibitor. It is an organophosphate active metabolite of the insecticide parathion.

paraoxon

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List the key organs in biotransformation

liver > lung/kidney/intestine

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Two phases in biotransformation pathways:

Phase 1: make the toxicant more (blank)
Phase 2: conjugate with a (blank) endogenous agent

soluble; soluble

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Acetaminophen has a toxic intermediate that binds with (blank) and other compounds in the body. If you deplete (blank) due to too much acetaminophen, you will have major problems with the high dose intermediate binding to other compounds and inducing cell death.

glutathione; glutathione

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T/F: Biotransformation does not effect the rate of clearance of compounds, and can occur at any point during the compound’s journey from absorption to excretion

False, it can drastically effect the rate of clearance of compounds; can occur at any point from absorption to excretion

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In what ways can AGE cause differences in response to a drug?

``` underdeveloped excretory mechanisms underdeveloped biotransformation enzymes underdeveloped BBB greater % of water in infants greater skin permeability stomach is less acidic ```

Genetics can also be a factor that changes how individuals respond to the same drug. Give an example with N-acetyltransferase and an example with thiopurine S-methyltransferase

with N-acetyltransferase, some races/populations have slower acetylation, while others have fast acetylation with TPMT, people with high levels of the enzyme respond poorly to chemo bc they conjugate the drug too quickly before it can act

What population to these characteristics apply to? ``` Impaired renal and respiratory function Less efficient drug metabolizing enzymes More fat as % of body wt Lower water content Lower cardiac output and perfusion Lower plasma albumin ```

the elderly

What is the treatment for CO poisoning?

remove the exposure and give O2

Why is CO toxic?

forms carboxyhemoglobin, which does not carry oxygen, so decreased O2 transfer of O2Hb

What is the treatment for SO2 poisoning?

supportive respiratory care

What does SO2 do to the body? How is it toxic?

forms sulfuric acid on moist membranes, leading to irritation of eyes, mucous membranes, skin; significant lung toxicity causing bronchiolar constriction and bronchospasms

Where is NO2 found in the environment?

given off w fires and in large amounts in grain silos

How is NO2 toxic?

deep lung irritant; exposure to high levels for even short periods can cause pulmonary lesions, pulmonary edema and death

How is ozone toxic?

deep lung irritant - pulmonary edema, causes airway inflammation and hyper-sensitivity

How to treat ozone poisoning?

supportive respiratory care antibiotics bronchodilators

What type of toxin are organophosphates and carbamate insecticides? What symptoms do they cause?

cholinesterase inhibitors; diarrhea, urination, miosis, bradycardia, anxiety, seizures, lacrimation **death usu from respiratory depression

What's the difference between organophosphates and carbamates in terms of their biochemical action?

organophosphates bind irreversibly, and carbamates are reversible inhibitors

(blank )is an organophosphate insecticide. If ingested or absorbed, it is converted to paraoxone, an inhibitor of cholinesterase Delayed toxicity

Parathione

How do you treat insecticide poisoning?

atropine IV until wheezing and bradycardia are gone or 2-Pam w/i 24 hours to reverse the effects of OPs at all sites

Leading cause of toxic drug ingestions in the United States. These can lead to hepatic toxicity and death when ingested in quantities of 150 mg/kg or more.

Acetaminophen

Acetaminophen is metabolized to a toxic intermediate that can deplete hepatic (blank). In infants and adults, this can lead to (blank) damage

glutathione; liver

List some ways that you can treat acetaminophen poisoning

oral activated charcoal | oral N-acetylcysteine (Mucomyst)

Because most toxins do not have specific antidotes, what are some ways to treat them?

``` activated charcoal emesis gastric lavage (pump) urinary excretion (alkalinization) dialysis ```

Give (blank) for reconstitution of cholinesterase activity to treat organophosphate poisoning.

2-Pam

Give (blank) for formaldehyde poisoning to form hexamethylenetetramine

ammonia

What are some effects of lead poisoning? How do you get lead poisoning?

multisystem effects: decreased development and mental retardation in children, peripheral neuropathy, nephrotoxicity, and anemia; inhaled and ingested, binds to erythrocytes and deposited in bone

How to treat lead poisoning?

identify/eliminate exposure | metal chelators such as calcium EDTA and dimercaprol to bind metal and enhance its excretion

Describe how methanol is metabolized

Methanol --> formaldehyde --> formic acid --> C02 + H20 leading to metabolic acidosis and tissue injury

What is the treatment for methanol poisoning?

supportive measures, airway correct acidosis w bicarbonate fomepizole to block alcohol dehydrogenase folic acid to enhance breakdown of formic acid ETOH to competitively inhibit the enzyme

This compound was added to ginger/alcohol to make it more tolerable. Eventually caused loss of use of hands and feet due to neurotoxic effects

TOCP (tri-o-cresyl phosphate)

This compound was mixed with engine oil to spray roads, barns and stables. Eventually it began to cause disease and miscarriages, eye, skin mucous membrane irritation, nauseau, vomiting, polyneuropathies...

Dioxin

This is the substance most frequently involved in human poison exposures in the US. Also causes the largest number of deaths.

analgesics (pain killers)

Known impacts and known probabilities

risk

Known impacts and unknown probabilities

uncertainty

Unknown impacts and unknown probabilities

ignorance

Odors: Bitter almonds: Mothballs: Garlic: Peanuts: Carrots: Rotten eggs: Wintergreen: Gasoline: Fruity: Pears:

``` cyanide camphor organophosphates rodenticide water hemlock sulfur dioxide methyl salicylates hydrocarbons DKA, isopropanol chloral hydrate ```

Most poisonings are by (blank) and most occur at home

ingestion

The most commonly reported poison? The least commonly reported? Which is associated with the most deaths? Which is associated with the least deaths? The number one poisonous killer?

analgesics; alcohol; analgesics; hydrocarbons; carbon monoxide

Why would you want an EKG with toxemia?

to look for conduction delays and ischemia

Why would you want a CMP with toxemia?

to calculate the anion gap and osmolality

Why would you want tylenol aspirin levels?

to measure frequency of abuse and co-ingestion

What should you always check with vitals?

blood sugar

What is used for the malnourished?

thiamine

What is reserved for pts who overdose with benzodiazapenes?

flumazenil

When is gastric lavage used?

with moderate to severe overdose and within an hour of ingestion **not used with ingestion of corrosives

When is activated charcoal used?

for GI decontamination, superior to lavage, used in toxic ingestions w/i one hour of ingestion

When are cathartics used in GI contamination?

with charcoal to enhance elimination **not effective alone

With poisoned patients, what is the FIRST thing you should do?

check airway, breathing, circulation