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Pharmacology > Toxicology > Flashcards

Toxicology Flashcards

1
Q

what is occupational toxicology?

A

deals with the chemicals found at the work place. The

workplace must follow threshold limit values (TLV)

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2
Q

define Hazard

A

is the ability of a chemical agent to cause injury in a given situation or setting; the conditions of use and exposure are primary considerations.

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3
Q

define Risk

A

The expected frequency of the occurrence of an

undesirable effect arising from exposure to a chemical or physical agent.

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4
Q

define Bioaccumulation

A

If the intake of a long-lasting contaminant by an
organism exceeds the latter’s ability to metabolize or excrete the
substance, the chemical accumulates within the tissues of the
organism.

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5
Q

define biomagnification

A

although the concentration of a contaminant may
be virtually undetectable in water, it may be magnified hundreds or thousands of times as the contaminant passes up the food chain.

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6
Q

name acute toxic effect toxins?

A

cyanide
coniin
fuge
ethanol

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7
Q

name subchronic toxic effect toxins?

A

eye/methanol phalloidin (3 days)

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8
Q

name chronic toxic effect toxins?

A

vinyl chloride: hepatic angiosarcoma

Ethanol: cirrhosis

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9
Q

name reversible toxic effect toxins?

A

N-hexane: regeneration of peripheral axons

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10
Q

name irreversible toxic effect toxins?

A

Aminoglycosides - no regeneration of central axons

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11
Q

what are predictable toxic effects?

A

dose/effect relationship

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12
Q

what are non-predictable toxic effects?

A

immunological
genetic background
idiosyncrasy (behavior) (G6PD)

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13
Q

pathway of exposure?

A
  1. exposure pathway: reaching individual
  2. toxicokinetic: reaching target site within body
  3. toxic effect: depends on dose and time
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14
Q

what influences dose at target site?

A

individuals may react different, like bodyweigt

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15
Q

Routes of exposure?

why is it important?

A

dermal
inhalation
oral inngestion
injection

related to tissue specific toxic response, they may be local or systemic

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16
Q

why is the timeframe of exposure important?

A

duration and frequency contribute to dose, acute vs chronic

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17
Q

what is the key concept in toxicology?

A

DOSE!!

All things are poisonous, only the dose makes it non-poisonous. all chemicals, synthetic or natural may be toxic.

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18
Q

What is the dose-response relationship?

A

A key concept in toxicology is the quantitative relationship between the concentration of a xenobiotic and the magnitude of the biological effect in produces

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19
Q

4 important processes that control the amount of a chemical that reaches the target site

A 
ATME 
absorption 
tissue distribution 
metabolism 
excretion
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20
Q

beneficial and toxic dose of aspirin?

A

beneficial: 300-1000 mg
toxic: 1000 - 30 000mg

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21
Q

beneficial and toxic dose of vitamin A?

A

beneficial: 5000 U/day
toxic: 50 000 U/day

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22
Q

beneficial and toxic dose of oxygen?

A

beneficial: 20% (air)
toxic: 50-80% (air)

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23
Q

dose dependent functions of aspirin?

A

<300mg: blocks platelet agg.
300-2400mg/day: antipyretic and analgetic effect
2400-4000mg/day: anti-inflammatory effects

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24
Q

when is plasma salicylate concentration toxic?

A

50-80 mild - hyperventilation
80-110 moderate - fever, dehydration, met. acidosis
110-160 severe - vasomotor collapse, coma, hypoprothrombinemia
160 and above is lethal - renal and respiratory failure

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25
Q

which organs can do biotransformation?

A

liver (primary site of metabolism)
kidney
lung
GI

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26
Q

toxins causing fatty liver?

A

triglyceride accumulation
hydrazine, tetracycline
CCI4 - necrosis
ethanol repeated exposure

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27
Q

toxins causing cytotoxic damage to liver

A

cocaine, allyl alcohol - periportal necrosis
CCI4, paracetamol - centrilobular necrosis
TNT - massiv liver necrosis
Phalloidin - ischemia and swelling of sinusoid cells
furosemide - biliary excretion saturated at high dose

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28
Q

General management of poisoned patient

A

ALL patient should be managed as it they have potentially life-threatening intoxication even if they seem fine. initial approach is the same irrespective of toxin

  1. emergency care
  2. decontamination
  3. antidotes
  4. Enhancing elimination of toxins
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29
Q

diagnostic approach to intoxication

A
  1. clinical signs
  2. ECG
  3. Lab test analysis
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30
Q

what is to be done during the emergency stage of treatment?

A
  1. Initial assessment and stabilization
  2. recognition of poisoning
  3. identification of agents involved
  4. assessment of severity
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31
Q

the critical care ABCDEF

A 
A: airway protection 
B: oxygenation/ventilation 
C: treat arrhythmias 
D: hemodynamic support
E: treatment of seizures 
F: correction of temperature, abnormalities
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32
Q

Decontamination of GI?

A

NOT in unconscious patients, poisoned with corrosive agents (acid/bases), petroleum distillate or convulsant.

  1. induce emesis (syrup ipecac or rarely apomorphine)
  2. gastric lavage (protect the airway)
  3. whole bowel irrigation with gastric tube
  4. catharsis (not if paralytic ileus)
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33
Q

How long to do eye decontamination?

A

at least 20 minutes

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34
Q

how to do skin decontamination?

A
  1. remove clothing and seal them in double bags

2. wash the kin area that was in contact with clothes with soap and water

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35
Q

how can you enhance elimination of poison?

A

GI: multiple doses activated charcoal or cholestyramine in digital intoxication

Kidney: forced diuretic but high risk of lung edema

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36
Q

extra corporal removal of toxins?

A
  1. Dialysis (peritoneal, hemolysis) only for water-soluble molecules wit low molecular mass and don’t bind plasmaproteins strongly (alcohol, antibiotics, HM, salicylates, benzos)
  2. Hemoperfusion - removing drugs by passing the blood through an adsorbent material and back to the patient
  3. Plasmapheresis
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37
Q

mechanism of specific antidotes?

A
  1. Binding the poison
  2. Inhibit distribution
  3. Inhibit formation of toxic metabolites
  4. Promotes detoxification
  5. Competitive inhibitors
  6. Agents promoting regeneration of target cells
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38
Q

specific antidote: heavy metals (HM)?

A

chelating agents

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39
Q

specific antidote: cholinesterase blockers?

A

Atropin

Enzyme reactivators - Toxogonin and PAM

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40
Q

specific antidote: Cyanide?

A

Oxidants producing met-hemoglobin

Co-EDTA

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41
Q

specific antidote: Methemoglobin

A

Methylene blue

Thionin

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42
Q

specific antidote: snake venom

A

specific antisera

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43
Q

specific antidote: methanol, ethylene glycerol

A

ethanol

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44
Q

specific antidote: coumarines

A

vitamin K

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45
Q

specific antidote: opiates

A

Naloxone

46
Q

specific antidote: paracetamol

A

acetylcystein

47
Q

specific antidote: cardiac glycosides

A

digoxin antibodies

48
Q

specific antidote: CO

A

O2

49
Q

specific antidote: benzodiazepines

A

flumazenil

50
Q

chelators?

A

Dimercaprol - gold, bismuth, arsenic, encephalopathy
Succimer - lead, arsenic and mercury poisoning
Penicillamine - copper intoxication
EDTA calcium disodium - lead poisoning
Deferoxamine - iron poisoning

51
Q

what do you give in severe lead intoxication?

A

Dimercaprol with NaCaEDTA

52
Q

What to give in encephalopathy induced by inorganic lead or bismuth

A

Dimercaprol

53
Q

what is given in lead poisoning but not in encephalopathy?

A

Succimer or DMPS

54
Q

recommended max dose of arsenic?

when is it dangerous?

A

child: 14 ug
adult: 14 ug

healt threat at 50 ug

55
Q

arsenic pharmacodynamics

A

inhibit enzymes via sulfhydryl binging inhibiting oxidative phosphorylation

56
Q

distribution of arsenic`

A

soft tissues mostly liver and kidney

57
Q

what is the acute lethal dose of arsenic?

A

70-200mg or 1mg/kg/day

58
Q

acute effects of arsenic?

A
  1. gastroenteritis
  2. hypovolemic shock
  3. CNS symptoms
59
Q

weeks and months after arsenic poisoning?

A

weeks: peripheral neuropathy
months: transverse white striate on the nails

60
Q

chronic effects of arsenic poisoning?

A
  1. weakness
  2. peripheral neuropathy
  3. anemia
  4. liver and kidney damage
  5. skin changes
  6. hyperkeratosis
  7. hyperpigmentation
  8. cachexia
61
Q

treatment in arsenic poisoning?

A
  1. supportive care
  2. dimercaprol
  3. calcium sodium edetate
62
Q

lead distribution?

A

binds to erythrocytes

inorganic: soft tissue, redistribution in bones
organic: liver and CNS

63
Q

lead half-life?

A

tissue 12 months

bones 20 years

64
Q

acute effect of lead poisoning?

A

very rarely but encephalopathy may occur acutely with hemolytic anemia and spasmic ileus

65
Q

chronic effect of lead poisoning?

A

Blood: inhibit heme synthesis and basophil stripping
GI: loss og appetite, lead colic, gingival lines
Nervous system
Bones: growth retardation in children

66
Q

therapy of acute lead poisoning?

A

FIRST give dimercaprol and 4h later give CaNaEDTA IV

67
Q

therapy of chronic lead poisoning?

A

CaNaEDTA IV for 5 days then succimer

68
Q

which drug can remove lead from bones?

A

NaCaEDTA

69
Q

major effect and therapy of organic lead poisoning?

A

Major effect: CNS (delirium, convulsion, brain edema)

Therapy: chelators has no effect

70
Q

CO poisoning route?

A

inhalation

71
Q

normal CO levels in humans?

A

COHb is normally at 1% and 5-10% in smokers

72
Q

Mechanism of CO poisoning?

A

binds Hb 250 higher affinity then O2 and decreases the O2 carrying capacity by forming carboxyhemoglobin

73
Q

what happens to the Hb O2 dissociation cure in CO poisoning?

A

shifts to LEFT

74
Q

% of CO giving the different symptoms?

A

15% may produce symptoms
40% lead collapse
60% death

75
Q

treatment of CO poisoning?

A
  1. remove source
  2. maitane ventilation
  3. administer O2
  4. hyperbaric O2 treatment
76
Q

forms of mercury entering body?

A

Elementary mercury - respiratory
mercury salts - GI
organic Hg (methyl Hg) - GI, skin, respiratory

77
Q

acute effects of mercury poisoning?

A

elementary: pulmonary edema
salts: corrosive hemorrhagic gastroenteritis –> Hypovolemic shock, ANT, oliguric kidney failure, anuria

78
Q

treatment of acute mercury poisoning?

A

dithiol chelators

79
Q

major effect of chronic mercury poisoning?

A 
neuropsychiatric disturbance
memory loss 
fatigue 
insomnia 
depression/anger 
loosing teeth 
kidney damage 
acrodynia in children
80
Q

Formaldehyde poisoning effect?

A

protein precipitation - necrotic effect

81
Q

therapy for formaldehyde poisoning

A

milk, water, gastric lavage, hemodialysis

82
Q

what NOT give in formaldehyde poisoning?

A

Don’t give sulfonamides - causes precipitation in kidney tubules

83
Q

Halogenated aliphatic hydrocarbon therapy if monohalogenated methanes?

A

alkali therapy in case og acidosis

84
Q

what is the lethal dose of halogenated aliphatic hydrocarbon CCL4?

A

20-30ml

85
Q

examples of aromatic hydrocarbons?

A 
Benzen
Toluene
Xylene 
Phenol
Nitrobenzen 
Aniline 
Dinitrophenol
Dinitroortocresol
86
Q

phenol intoxication treatment?

A

gastric lavage
purgation with cooking oil
activated charcoal

87
Q

nitrobenzen and aniline intoxication therapy?

A

reduce methemoglobinemia
drink milk
oil

88
Q

what can provoke urinary bladder papilloma or cancer?

A

benzidine, naphthylamine, minophenydile

89
Q

lethal dose of dinitroortocresol?

A

1g

90
Q

Dinitrophenol and dinitroortocresol intoxication therapy?

A

cold bath
O2 inhalation
0.9% NaCl
Glucose infusion

91
Q

lethal dose methaldehyde?

A

adults: 4g
children: 0.1-0.5g for children

92
Q

enzyme converting methanol to formaldehyde?

A

ethanol (alcohol) dehydrogenase

93
Q

enzyme converting formaldehyde to formic acid?

A

aldehyde dehydrogenase

94
Q

symptoms of methanol intoxication?

A

has a latency period (8-30h), if ingested with ethanol it gives ethanol intoxication sumptomes

met. acidosis
abdominal pain
blindness

95
Q

methanol and glycoles therapy?

A
  1. ethanol 10g/hr IV or orally 20-30cl drink every 3-4h

2. Fomepizole IV

96
Q

what is the mechanism of divalent glycols?

Name two

A

Diethylene glycol

Ethylene glycol

96
Q

what is the mechanism of divalent glycols?

Name two

A

Diethylene glycol
Ethylene glycol

Alcohole dehydrogenase converts them to glycol aldehyde then to oxalic acid which causes tubular necrosis

97
Q

Inocybe mushroom poisoning therapy?

onset time?

A

atropin 1-2mg every 30 min

RAPID onset

98
Q

Amanita muscaria and pantherina mushroom poisoning therapy?

Onset time?

A

RAPID onset

treat symptoms but DO NOT give atropin

99
Q

Amanita phalloides, vorisa, vera mushroom poisoning therapy and onset time?

A

Delayed onset

  1. protect liver and kidney
  2. high dose G-penicillin
  3. Silibinin
  4. N-acetylcystein
100
Q

acid intoxication therapy?

A
  1. NO emesis and NO gastric lavage
  2. dilute the acid in stomach (not milk)
  3. oral local anesthetics
  4. morphine, atropine, glucocorticoids
  5. drop infusion 5% NaHCO3 or Na lactate
101
Q

oxalic acid intoxication treatment?

A

CaCl2
Ca gluconate IV
fluids
+ treat acidosis

102
Q

what happens to iron in MH intoxication?

A

Ferro-Ferri (2+ to 3+)

103
Q

lethal dose MH?

A

60-80%

104
Q

what is verdoglobin?

A

irreversibly changes of Hb where the porphyrin ring oxidizes and split

105
Q

what may be seen in RBC in MH intoxication?

A

Heinz bodies

106
Q

what are the bacteria causing food poisoning?

A

Salmonella
Proteus vulgaris
E.coli
B. cereus

107
Q

food poisoning treatment?

A

gastriv lavage
activated charcoal
replacement of volume and electrolytes

108
Q

lethal dose botulotoxin?

A

0.001-0.002 mg/kg

109
Q

botulism therapy?

A

Antitoxin ABE
purge with casteroil + neostigmine
transfusion

Pharmacology (3 decks)

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