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Pharmacology Exam 5 > 69 - Toxicology I > Flashcards

69 - Toxicology I Flashcards

1
Q

What is a poison?

A

Any chemical that is physiologically harmful when administered to a living organism

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2
Q

What does a poisoning depend on?

A

Poisoning is situational and quantitative in nature
- Any substance at a specific dose (or time) can be harmless, but the same substance in a different circumstance can be toxic

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3
Q

How is a drug labeled if it is created, by design to induce physiological harm?

A
  • The word “DANGER” plus the word “POISON”

- A display of the skull and crossbones icon

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4
Q

What is the primary determinant of toxicity?

A

Dose

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5
Q

What else does toxicity depend on?

A

Time

The toxic effects of chemicals in physiological systems are also dependent on the duration of time that these chemicals are present

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6
Q

Why is it important to study toxicology? How does it serve humankind? (two ways)

A
  • To protect humans and other organisms from the adverse effects of toxicants (e.g. chemical warfare, pollution, prescription drugs, etc.)
  • To serve as a means to develop improved toxicants (e.g. pesticides, antibiotics, etc.)
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7
Q

What is toxicology?

A

It is a science developed from a combination of several other sciences:

  • pharmacology (adverse drug responses)
  • pathology (disease and death)
  • chemistry (organic interactions)
  • epidemiology (hazards and risks)
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8
Q

How can you measure toxicology?

A
  • mortality
  • teratogenicity
  • carcinogenicity
  • mutagenicity
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9
Q

As a whole, what is the goal of toxicology?

A

As a whole, is therefore a science aimed at enhancing the quality of life

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10
Q

How many deaths is toxicology responsible for?

A

Toxicants are responsible for at least 30,000 accidental deaths annually

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11
Q

What do children become poisoned from most commonly?

A

plants, cosmetics, salicylates, hydrocarbons, detergents and acetaminophen

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12
Q

What do adults become poisoned from most commonly?

A
  • barbiturates, carbon monoxide, salicylates, alcohol, narcotics and acetaminophen
  • Work place accidents associated with chemicals used in manufacturing (e.g., farming - insecticides)
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13
Q

What is acute toxicity?

A

Acute Toxicity

  • Ability of a substance to cause severe biological harm or death soon after a single exposure
  • Defines ‘intrinsic toxicity’
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14
Q

What is chronic toxicity?

A

Chronic Toxicity
- Adverse effects as a result of repeated chemical dosing on a daily basis or exposure to the chemical for a majority of an organism’s lifespan

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15
Q

What is LD50?

A

Lethal dose

  • LD50, dose at which 50% of animals tested die
  • TD50, dose at which 50% have toxicity
  • Measure of harmfulness
  • Legally, a ‘poison’ has an LD50 ≤ 50mg/kg bwt
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16
Q

What is TI?

A

Therapeutic index

  • LD50/ED50
  • The larger the number, the safer the drug***
  • Measure of relative safety
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17
Q

How do you calculate the TI?

NEED TO KNOW ***

A

TI = LD50/ED50

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18
Q

What is one of the most toxic compounds we know of?

A

Botulinum toxin

Smallest LD50 we know of

19
Q

What is ALD?

A

ALD, average lethal dose

Estimated from accidental deaths in humans

20
Q

What is the primary determinant of toxicity?

A

NEED TO KNOW ***

Dose **

Also ask about timing - how log has the agent been present in the body?

21
Q

How do you clinically manage poisoning?

A
  • Regardless of the cause, rapid measures are called for in every case of poisoning
  • Whatever you do, do it quickly ***
  • ABCs
  • Try to remove the drug from the body - decrease the dose and decrease the time of exposure
22
Q

How do you treat an unconscious patient specifically?

A

Several general antidotes available to treat patient upon presentation at the hospital:

  • glucose/insulin (diabetic shock/hypoglycemia)
  • naloxone (narcotic overdose - opioid antagonist)
  • you can save their life, but nothing bad will happen if you’re wrong
23
Q

What is the next step?

A

Identify the poison

  • Patient history
  • Lab testing (QUICKLY)
  • Tests take time, so you might not be able to wait for results
24
Q

What are toxidromes?

A

Known toxicology standards

Will talk about it more later on

Comparison of drug or chemical responses of the patient with known toxicology standards (toxidromes) and known adverse responses

25
Q

What is one option for drug removal?

A

Emesis
- A way of removing unabsorbed toxicants from the GI tract

Ways of inducing emesis

  • Mechanical
  • Apomorphine [Apokyn®]
  • Syrup of Ipecac [emetine (methylcephaeline) and cephaeline]
26
Q

What are the contraindications of drug removal via emesis

A
  • Petroleum hydrocarbon solvent – chemical pneumonitis
  • Caustic acid or alkali agent (rupture)
  • Seizing or comatose patient
27
Q

What is another option for drug removal via emesis?

A

Gastric lavage

  • This is an early step in the treatment of intoxication
  • After application of a topical anesthetic, a tube is inserted through the nose or mouth and into the stomach
  • Stomach contents are irrigated and removed using suction
  • “pumping the stomach”
28
Q

What is the last option for drug removal?

A

Activated charcol

  • Administered orally in water
  • Very large surface area allows for binding of organic toxicants which prevents absorption
  • Often induces emesis which can be messy and problematic
29
Q

What are the other options for drug removal?

A
  • Cathartics (Promotes rapid movement and elimination of poison through GI tract)
  • Diuresis
  • Water dilution
  • Demulcents
  • Hemodialysis
30
Q

What are the four antidotes that chelate toxicants?

A
  • Organophosphates (acetycholinesterase inhibitors)
  • Cyanide
  • Toxins (botulinum toxin)
  • Heavy metals
31
Q

Describe the use of organophosphates to chelate toxicants

A

Acetycholinesterase inhibitors
- Pralidoxime (Protopam, 2-PAM) is a nucleophilic reagent that covalently binds to organophosphates and permits rapid excretion

Usually administered with atropine to block muscarinic effects of parasympathetic nervous system

32
Q

What are some types of poisoning that could be treated by organophosphates?

A

Used to treat poisoning* by:

  • Insecticides: malathione, parathione, etc.
  • Tabun: Ethyl N,N- dimethylphosphoramidocyanidate
  • Sarin: Isopropylmethylphosphofluoridate
  • Soman: 1,2,2-Trimethylpropylmethyl-phosphonofluoridate
  • VX: o-Ethyl-S-(2[di-isopropylamino]ethyl) methylphosphonothiolate
  • GF: Cyclohexylmethyl-phosphonofluoridate
33
Q

Describe the use of cyanide to chelate toxicants

A
  • Binds to and deactivates cytochrome c oxidase (aa3) in mitochondrial membranes of all cells. Final transport of electrons from aa3 to oxygen can not be completed. As a result, the electron transport chain is disrupted and the cell can no longer produce ATP for energy. CNS and cardiac tissue are particularly affected.
  • LD50=2mg/kg, producing death in 1-15 minutes
  • Administer amyl nitrite, sodium nitrite and sodium thiosulfate with O2 and whole blood to convert hemoglobin to methemoglobin; this combines with cyanide to form nontoxic cyanmethemoglobin and thiocyanate (LD50 increases 5-fold)
34
Q

Describe the use of toxins such as botulinum toxin to chelate toxicants

A

Most potent poison known, rapidly absorbed and prevents ACh release from nerve terminals; most common: respiratory depression

This can treat the “ABCs”

Mortality is reduced from 70% to 10% when treated

35
Q

Describe the use of heavy metals to chelate toxicants

A

Chelators (BAL, EDTA, DMSA, DMPS, calcium EDTA, deferoxamine) complex with Hg, Pb, As, Fe and/or Ag making them inert and increasing renal excretion

36
Q

What is the DMSA agent (Chemet*)?

A

Indicated for the treatment of arsenic, mercury or lead poisoning ***

37
Q

What are the adverse reactions of DMSA (Chemet*)?

A
  • Chills, fever, diarrhea, loose stools, loss of appetite, nausea and vomiting, skin rash
  • Patients should be informed that succimer will cause urine, sweat and feces to have an unpleasant odor
38
Q

Describe the dosing for DMSA (Chemet*)

A

For adults and children ≥12 years of age
- 10mg/kg, PO, q8h for 5 days

For children 1-11 years of age

  • 10mg/kg, PO, q8h for 5 days
  • The same dose is then given q12h for the next 14 days, for a total of 19 days of therapy
  • May sprinkle on soft food or in juice to improve palatability.
39
Q

What is another treatment option for botulinum toxin poisoning?

A

In US, botulinum antitoxin (equine) is available from the CDC via state and local health departments

The licensed trivalent antitoxin contains neutralizing antibodies against botulinum toxin types A, B, and E, the most common causes of human botulism.

Heptavalent is also now available – recognizes all types of boutulinum toxin.

40
Q

What is a cyanide antidote kit?

A

Provides three agents in the following order

  • Small inhaled dose of amyl nitrite
  • IV sodium nitrite
  • Sodium thiosulfate

Know this order and the things in the kit ***

NITRATES AND THIOSULFATE***

41
Q

Describe an anti-freeze poisoning (ethylene glycol poisoning) or other alcohol poisoning. What is the treatment?

A
  • Ethylene glycol = anti-freeze
  • Methanol or isopropyl alcohol can have similar effects
  • These agents convert into acetaldehyde and acetate (poisonous)

Treatment

  • Ethanol administration (to competitively prevent alcohol dehydrogenase)
  • Alcohol dehydrogenase is the enzyme that converts any type of ethanol to the poisonous compounds
  • Hemodialysis can also be an adjunct (life saving) measure
42
Q

What is the use of fomepizole?

A

Alcohol overdose (any type)

  • It blocks alcohol dehydrogenase***
  • Alcohol dehydrogenase is the enzyme that allows for the conversion of ethanol/methanol or any other alcohol into the poisonous acetaldehyde and acetate
  • Fomepizole had few side effects, and is considered the drug of choice for antidotal therapy for ethylene glycol or methanol toxicity
  • Prevents production of toxic metabolites ***
43
Q

What is the therapy of carbon monoxide poisoning?

A
  • Artificial respiration with pure O2 to promote displacement of CO
  • Hyperbaric oxygen chamber if symptomatic
44
Q

What are the symptoms of carbon monoxide poisoning?

A
  • Cherry red appearance of the lips and gums ** (high level of poisoning)

Others include headache, dizziness, fatigue, weakness, convulsions, coma, respiratory collapse, death

Pharmacology Exam 5 (5 decks)

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