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Toxicology Flashcards

1
Q

What is descriptive toxicology and mechanistic toxicology and regulatory toxicology

A

It tells what happened that resulted in the destruction of cells,tissues, organs or death as a whole

It is the pathway that causes the problems due to poisoning

Regulatory toxicology is the branch of toxicology (the study of adverse effects of chemicals) that uses scientific knowledge to develop regulations and other strategies for reducing and controlling exposure to dangerous chemicals

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2
Q

All substances are toxic if taken in the wrong quantities and a poison is a substance not a drug true or false

A

True

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3
Q

What is forensic toxicology

A

Forensic toxicology = analytical chemistry + fundamental toxicology
•Forensic toxicology is defined as the application of toxicology for the purposes of the law.
•Clinical toxicologists: are clinicians who treat poisoned patients by drugs and other chemicals and develop new techniques for them

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4
Q

So Toxicology is the study of how toxicants:
•enter the organism
•Influence the organism
•are eliminated from (leave) the organism
True or false

A

True

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5
Q

What is toxicokinetics and what does it involve

A
  • Toxicokinetics (Determines the no. of molecules that can reach the receptors)
  • Uptake
  • Transport
  • Metabolism & transformation
  • Sequestration
  • Excretion
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6
Q

What is toxicodynamics and what does it involve

A

Toxicodynamics (Determines the no. of receptors that can interact with toxicants)
•Binding
•Interaction
•Induction of toxic effects

Relationship between dose and intended pharmacological response and resultant toxicological response.
•“All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy” (Paracelsus)
•Eg. Acetaminophen and ethanol

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7
Q

What affects toxicokinetics

A

Time course of blood and tissue concentration profile.
•Toxicokinetics and factors affecting/modifying action of poisons include:
•Dose/concentration
•age,
•route of absorption/administration,
•frequency and rate of administration,
•state of poison(liquid,solid,gas,parent form,metabolite of the parent form)
•if person is healthy or unhealthy already
•tolerance, idiosyncrasy etc.

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8
Q

The degree and spectra of responses depends on

A

The dose and the organism and exposure conditions with description of the dose

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9
Q

What is graded dose response and quantal dose response

A

Graded response - increasing by specific doses and expecting or predicting specific responses

Quantal- Not easy to predict. Only LD50(median lethal dose)is needed or a specific parameter
Example:patient drug and metabolites,acute versus chronic exposure

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10
Q

What is LD50

A

The cumulative proportion of the population responding to a certain dose is plotted per dose 10-30 fold variation within a population
•If Mortality is the response, the dose that is lethal to 50% of the population (LD50 ) can be generated from the curve
•Different toxicants can be compared: lowest dose is most potent

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11
Q

If rate of uptake is more than elimination what happens

A

There will be accumulation and toxic effect

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12
Q

How are toxicants taken up?

A

Passive diffusion
•Facilitated transport: Calmodulin for facilitated transport of Ca
•Active transport: P-glycoprotein pump for xenobiotics
•Ca-pump (Ca2+ -ATPase)
•Pinocytosis: Airborne toxicants across alveoli cells
•Carrageenan across intestine

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13
Q

In uptake by passive diffusion what happens

A

Uncharged molecules may diffuse along conc. gradient until equilibrium is reached
• it is Not substrate specific
•Small molecules of < 0.4 nm (e.g. CO, N20) can move through cell pores
•Lipophilic chemicals may diffuse through the lipid bilayer

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14
Q

When equilibrium is established there is no passive diffusion true or false

A

True

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15
Q

Which mediums are toxins transported thru

A 
Transport
•Blood
•Lymph, haemolymph
•Water stream in xylem
•Cytoplasmic strands in phloem
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16
Q

Where is lead deposited at

A

Bone teeth brain

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17
Q

Where is CD or cadmium toxins deposited at

A

Kidney,bone,gonads

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18
Q

Where is OC or organochlorine and polychlorinated Biphenyls (PCB)deposited

A

Adipose tissue ,milk

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19
Q

Where is Organophosphate deposited

A

Nervous tissue

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20
Q

Where is aflatoxin deposited

A

Liver

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21
Q

Systemic toxicity most often involves the central nervous system (CNS) or the cardiovascular system. True or false

A

True
In local toxicity example, if you take a weak acid it can corrode the intestine or somewhere before it gets into systemic circulation and becomes systemic toxicity

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22
Q

What are the principles of detoxification

A

Convert toxicants into more water soluble form (more polar & hydrophilic)

  1. Dissolve in aqueous/gas phases and eliminate by excretion (urine/sweat) or exhalation
  2. Sequestrate in inactive tissues (e.g bone, fat)
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23
Q 
•Adverse effects can occur at the level of the molecule, cell, organ,  or organism
•Molecularly, chemical can interact with
Proteins        Lipids    DNA
•Cellularly, chemical can
•interfere with receptor-ligand binding
•interfere with membrane function
•interfere with cellular energy production
•bind to biomolecules
•perturb homeostasis (Ca)

True or false

A

True

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24
Q

With irritants the effect is limited to skin,nose, eye, ear ,mouth true or false

A

True

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25
Q

With aesthetic effects, the effect is on the Brain and spinal cord true or false

A

True

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26
Q

What is sequestration

A

Animals may store toxicants in inert tissues (e.g. bone, fat, hair, nail) to reduce toxicity
•Plants may store toxicants in bark, leaves, vacuoles for shedding later on
•Lipophilic toxicants (e.g. DDT) may be stored in milk at high concentration and passed to the young

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27
Q

How are toxins excreted

A

Gas (e.g. ammonia) and volatile (e.g. alcohol) toxicants may be excreted from the lung by simple diffusion
•Water soluble toxicants (molecular wt. < 70,000) may be excreted through the kidney by active or passive transport
•Conjugates with high molecular wt. may be excreted into bile through active transport
•Lipid soluble and non-ionised toxicants may be reabsorbed (systematic toxicity)

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28
Q

What is enterohepatic cycle

A

Secreted substances move back into the liver but are never excreted

Enterohepatic circulation refers to the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver.

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29
Q

When patient is poisoned what are the questions you ask

A 
Has this person been poisoned
•What is the identity of the poison
•How was it administered
•What are its effects
•Was it a dangerous or lethal amount
30
Q

Classes of toxic agents

A

Those for which a specific treatment or antidote exists and
•Those for which there is no specific treatment.
For the vast majority of drugs and other chemicals, there is no specific treatment; symptomatic medical care that supports vital functions is the only strategy.

31
Q

How to prevent further absorption of toxins

A

Emesis:syrup Ipecac or ipecac sodium ( to induce emesis and it takes 15-30 minutes) must be administered within one hour of being poisoned
b. Apomorphin (to induce emesis . Is given IV and takes 3-5minites to induce emesis.

  1. Gastric lavage: Accomplished by inserting a tube into the stomach and washing the stomach with water, normal saline, or one-half normal saline to remove the unabsorbed poison.
    •The procedure should be performed as soon as possible, but only if vital functions are adequate or supportive procedures have been implemented.
32
Q

If the time the patient has ingested the poison and the time hasn’t reached 30 minutes then try emesis. True or false

A

True

33
Q

How do ipecac and apomorphine work

A

It has a local irritant effect on the enteric tract and has effect on the chemoreceptor trigger zone (CTZ) in the area postrema of the medulla.

Apomorphine-Stimulates the chemoreceptor trigger zone (CTZ) and causes emesis.

34
Q

Which drug for emesis is unstable in solutions,must be prepared prior to use,not effective orally,must be given parenterally by subcutaneous route 6mg for adults and 0.06mg/kg for children

A

Apomorphine

35
Q

Which drug for
Emesis is a syrup Syrup of ipecac is available in 0.5- and 1-fluid ounce containers (approximately 15 and 30 ml)
•Takes 15 to 30 minutes to produce emesis
•The oral dose is 15 ml in children from 6 months to 12 years of age and 30 ml in older children and adults.
•Administer within 60 minutes of poisoning

A

Ipecac

36
Q

Chronic abuse of Ipecac can result in cardiomyopathy,ventricular fibrillation, and death. True or false

A

True

37
Q

What are the advantages of apomorphine

A

Advantage over ipecac: it can be administered to an uncooperative patient and produces vomiting in 3 to 5 minutes.

38
Q

What is a contraindication of apomorphine

A

•It is a respiratory depressant, therefore should not be used if the patient has been poisoned by a CNS depressant or if the patient’s respiration is slow and

39
Q

What are the contraindications of using emesis

A

If the patient has ingested a corrosive poison, such as a strong acid or alkali (e.g., drain cleaners), emesis increases the likelihood of gastric perforation and further necrosis of the oesophagus;
•if the patient is comatose or in a state of stupor or delirium, emesis may cause aspiration of the gastric contents;
•if the patient has ingested a CNS stimulant, further stimulation associated with vomiting may precipitate convulsions;
•if the patient has ingested a petroleum distillate (e.g., kerosene, gasoline, or petroleum-based liquid furniture polish), regurgitated

40
Q

Contraindications of gastric lavage

A

contraindications to this procedure generally are the same as for emesis; in addition, potential complication of mechanical injury to the throat, esophagus, and stomach.

41
Q

After absorption of toxins what are the next steps to take?

A

Chemical adsorption : Activated charcoal avidly adsorbs drugs and chemicals on the surfaces of the charcoal particles, thereby preventing absorption and toxicity. It binds to poisons and prevents them from being absorbed. Activated charcoal doesn’t go systemic
Chemical inactivation : Antidotes can change the chemical nature of a poison by rendering it less toxic or preventing its absorption.
Purgation : The rationale for using an osmotic cathartic is to minimize absorption by hastening the passage of the toxicant through the gastrointestinal tract.
Whole bowel irrigation: WBI may be considered in cases of acute poisoning by sustained-release or enteric-coated drugs and possibly toxic ingestions of iron, lead, zinc, or packets of illicit drugs.
•Should not be used routinely.

42
Q

Contraindications of gastric lavage are the same as emesis in addition to potential complication of mechanical injury, to the throat,stomach and oesophagus true or false

A

True

43
Q

Many chemicals are adsorbed by charcoal except ?

A

alcohols, hydrocarbons, metals, and corrosives- charcoal therefore is of little value in treating these poisonings.

44
Q

The effectiveness of charcoal also depends on the time since the ingestion and on the dose of charcoal; a charcoal-drug ratio of at least 10:1 should be attempted.

•Activated charcoal can also interrupt the enterohepatic
True or false

A

True

45
Q

How is formaldehyde poisoning treated

A

Formaldehyde poisoning can be treated with ammonia to form hexamethylenetetramine; sodium formaldehyde sulfoxylate can convert mercuric ion to the less soluble metallic mercury; and sodium bicarbonate converts ferrous iron to ferrous carbonate, which is poorly absorbed.

46
Q

Cathartics are indicated after the ingestion of enteric-coated tablets, when the time after ingestion is greater than 1 hour, and for poisoning by volatile hydrocarbons.
Example of cathartics are

A

•Sorbitol (most effective), sodium sulphate and magnesium sulphate

47
Q

Contraindications of purgation

A

Magnesium sulphate should be used cautiously in patients with renal failure or in those likely to develop renal dysfunction or with kidney problems
•Na+-containing cathartics should be avoided in patients with congestive heart failure.

48
Q

If ipecac is not able to induce emesis what do you do

A

Get it to come out by gastric lavage

49
Q

How is elimination of poison enhanced

A 
Biotransformation:
•Biliary Excretion
•Urinary Excretion
•Dialysis
•Antagonism or Chemical Inactivation of an Absorbed Poison
50
Q

Categories of drugs that usually cause problems

A

Analgesics Drug
•Chemical
•Environmental
•Although pharmaceuticals, drugs of abuse and ethanol (alcohol) are the most common poisons encountered in clinical and forensic toxicology, the possibility of poisoning with a wide range of other compounds has to be taken into account.

51
Q

Drugs that are usually abused are?
Drugs that are usually abused Appear in saliva almost immediately after drug administration by intravenous injection. True or false

A

Cocaine
Alcohol
Paracetamol: more toxic when co-administered with alcohol- liver toxicity.
•Treat with antioxidants and CYP 450 inhibitors
•N-acetyl cysteine

True

52
Q

Example of hypnotic or narcotic drugs is morphine .Morphine is a metabolite of codeine and can also be detected when codeine is abused.
•Morphine appears in saliva after the administration of morphine sulfate with a saliva :plasma ratio of 0.2.
True or false

A

True

53
Q

How is morphine abuse treated

A

Naloxone intravenous injection (antidote).
•Activated charcoal
•Purgation

54
Q

Heavy metals exert their toxic effects by combining with one or more reactive groups (ligands) essential for normal physiological functions. Heavy-metal antagonists (chelating agents) are designed specifically to compete with these groups for the metals and thereby prevent or reverse toxic effects and enhance the excretion of metals.

True or false

A

True

Example of chelating agents are dimercaprol and dimercaptosuccinic acid

55
Q

Mercury
•Readily forms covalent bonds with sulfur, and it is this property that accounts for most of the biological properties of the metal. When the sulfur is in the form of sulfhydryl groups, divalent mercury replaces the hydrogen atom to form mercaptides, X¾Hg¾SR and Hg(SR)2, where X is an electronegative radical and R is protein.
•Inhaled mercury unlike ingested mercury is completely absorbed by the lungs.

True or false

A

True

56
Q

The upper limit of a nontoxic concentration of mercury in blood generally is considered to be 3 to 4 mg/dl (0.15 to 0.20 mM)
True or false

A

True

57
Q

How is mercury treated

A

Prompt attention to fluid and electrolyte balance and hematological status
•Emesis may be induced if there is no corrosive injury
•Chelation therapy with dimercaprol: dimercaprol 5 mg/kg intramuscularly initially, followed by 2.5 mg/kg intramuscularly every 12 to 24 hours for 10 days.
•Penicillamine (250 mg orally every 6 hours) may be used alone or following treatment with dimercaprol.
•Chelate of dimercaprol is excreted into bile and urine whiles, penicillamine chelate is excreted only into urine.

58
Q

Chlorinated phenoxy acids are corrosive chemicals that damage the skin, eyes and respiratory and gastrointestinal tract. Ingestion of large doses causes vomiting, abdominal pain, diarrhoea, metabolic acidosis, pulmonary oedema and coma. True or false
And how is it treated

A

True

Alkalinisation of the urine to increase the excretion of 2,4-dichlorophenoxyacetic acid (2,4-D) and other chlorophenoxy compounds has proved an effective therapy.

59
Q

Arsenic is widely distributed in the environment, particularly in rocks, sediments and some water supplies. Organic forms of arsenic (e.g. arsenobetaine, arsenocholine) occur naturally in seaweed, fish and shellfish, but are mostly nontoxic. True or false

A

True

60
Q

How is arsenic detoxified and which type or arsenic is more toxic and how is it treated

A

Arsenic is metabolised in the liver to mono- and dimethylated species as a means of detoxification.

trivalent inorganic salts of arsenic (e.g. Sodium arsenite, NaAsO2) are the most toxic and may cause serious toxicity or death after acute ingestion of relatively small doses (200 mg).
•Treatment
•Dimercaprol and dimercaptosuccinic acid are chelating agents that sequester the arsenic away from blood proteins and are used in treating acute arsenic poisoning.

61
Q

Pesticides
•Compounds may or may not be toxic but solvent/vehicle used in preparation can be or potentiate toxicity.
•Organophosphorus compounds
•OP compounds are by far the most important class of pesticides, both in terms of worldwide usage and their toxicity to humans. True or false

A

True

62
Q

How do OP compounds work and how is it treated

A

They act by the irreversible inhibition of cholinesterase which are responsible for hydrolysing, and thereby deactivating, the neurotransmitter acetylcholine (AcCh).
Treatment
•Atropine and pralidoxime are effective antidotes in severe cases.
•In acute clinical poisoning, diagnostic

63
Q

•Botulism causes flaccid paralysis of muscles. It is caused by a neurotoxin, generically called botulinum toxin, produced by the bacterium Clostridium botulinum.
True or false

A

True

64
Q

How is botulism treated

A

Antibiotics for treatment, penicillin G sodium.

•Cathartics and enemas to remove unabsorbed botulinum toxin from the intestine.

65
Q

Symptoms of asprin poisoning

A

Symptoms: - tinnitus, hyperventilation, confusion, lethargy and sweating. Coma in very severe poisoning

66
Q

In aspirin poisoning Stimulation of respiratory centre complicates acid-base disturbances and also uncouples oxidative phosphorylation which may cause a metabolic acidosis. True or false

A

True

67
Q

How is aspirin poisoning managed

A

Management: measure plasma levels of salicylate (at 4-6 hours postingestion ), electrolytes and blood gases.
•Gastric lavage (up to 1 hour after ingestion) followed by activated charcoal administration.
•Severe poisoning requires urinary alkalinization, or haemodialysis in very severe poisoning.

68
Q

Symptoms of acetaminophen poisoning and how is it treated

A

Nausea and vomiting

Glutathione can inactivate the quinone.
•Reactive quinone covalently binds to thiol groups on the cell proteins and kills the cell.
•Acetylcysteine and methionine are potentially life saving antidotes.

69
Q

In acetaminophen poisoning

After 48-72 hours, relatively small amounts (10 g, 20-30 tabs) may cause fatal hepatocellular necrosis.

•At high doses, conjugation pathways are saturated → oxidation to a reactive quinone intermediate (N-acetylbenzoquinoneimine

True or false

A

True

70
Q

Symptoms of opioids and treatment

A

Cause coma, pinpoint pupils and respiratory depression.
•They are antagonized by naloxone (given iv) repeatedly until ventilation is adequate.
•Acute withdrawal syndrome may happen in opioid addicts

71
Q

Symptoms of tricyclic antidepressants and how it’s managed if abused

A

Respiratory depression, hallucinations, convulsions (anticholinergic effects)
•Cardiotoxicity

Management
•Correct hypoxia with oxygen
•Activated charcoal (within 1 hour)
•Sinus tachycardia may be controlled with intravenous diazepam or chlomethiazole.

•Gastric lavage is controversial
–Gastric contents may be pushed beyond the pylorus and increase the amount of drug absorbed.
–Struggle during lavage may c

72
Q

Symptoms of atropine abuse

A 
dry mouth,
blurred vision,
sensitivity to light,
lack of sweating,
dizziness,
nausea,
loss of balance,
hypersensitivity reactions (skin

Pharmacology (11 decks)

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