KING ABDUL AZIZ UNIVERSITY FACULTY OF PHARMACY PHARMACOLOGY & TOXICOLOGY DEPT . CORROSIVES LAB No.. 1 Date: ……………… The main toxic effect of corrosives consists of a local action on the tissues with which they come in contact. The local actions of various corrosives are much alike. The differences between compounds are chiefly in the intensity of the action. Some of them act mainly on the alimentary tract and to a very small extent on the skin. The degree of injury depends more upon the strength of the acid or alkali than upon the absolute quantity. A small quantity of a conc. acid does more damage than such larger quantities of dilute acid. Corrosion or direct destruction of the tissue occurs if the agent acts directly on the protoplasm. Chemical corrosion usually consists of simple inflammation followed by a layer of necrotic tissue. (A)The tissue protein is converted into acid proteinate, while dissolves in the conc. acid. 1
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KING ABDUL AZIZ UNIVERSITYFACULTY OF PHARMACY
PHARMACOLOGY & TOXICOLOGY DEPT.
CORROSIVES LAB No.. 1 Date: ………………
The main toxic effect of corrosives consists of a local action on the tissues with which
they come in contact. The local actions of various corrosives are much alike. The
differences between compounds are chiefly in the intensity of the action. Some of them
act mainly on the alimentary tract and to a very small extent on the skin. The degree of
injury depends more upon the strength of the acid or alkali than upon the absolute
quantity. A small quantity of a conc. acid does more damage than such larger quantities of
dilute acid.
Corrosion or direct destruction of the tissue occurs if the agent acts directly on the
protoplasm. Chemical corrosion usually consists of simple inflammation followed by a
layer of necrotic tissue.
(A)The tissue protein is converted into acid proteinate, while dissolves in the conc. acid.
(B)Haemoglobin is converted into dark acid haematin and is precipitated.
(C)The intense stimulation by acid causes reflex loss of vascular tone. In the alimentary
tract, the primary effect of corrosion by acids is perforation which may be delayed for
several weeks.
The secondary effect is destruction of the gastric glands and the tertiary effect is
starvation from constriction of the esophagus.
Death may result at any stage, but it occurs most frequently from shock or suffocation
due to intense swelling and edema of the throat structures.
N.B.
1
Organic acids such as phenol, oxalic acid, acetic acid and citric acids are weak
corrosives if compared with inorganic acids.
The area of contact is stained brown or black except in the case of nitric and picric
acids, which produce a yellow stain. Precipitated blood (coffee-ground material) is
frequently formed in the stomach.
Alkalis such as carbonates and bicarbonates does not produce corrosive effects in
equimolar concentrations to that of strong alkalis such as sodium, potassium or
ammonium hydroxide which are markedly corrosive in action. They dissolve protein
material, saponify lipids and extract water from tissues. Corroded areas are soft,
gelatinous and swollen.
I-POISONS ACTING LOCALLY
1- SULPHURIC ACID
Symptoms of Toxicity
A-Skin contact:
The local action on the skin may cause first, second or third degree of burns. The first
degree burns result in erythema and edema with hot, painful, red and swollen skin. In the
second degree burns, the damage is more severe, the edema is greater and vesicles and
bullae appear. Scars and depigmented area may result. Third degree burns are
characterized by sufficient damage to destroy the skin and to cause deep ulceration.
B-Ingestion:
When sulphuric acid is swallowed, there is intense pain in the GIT. The tongue swells
and vomitus is brown-coloured due to the blood and eroded tissues which it contains. The
secondary and tertiary effects result in emaciation, sunken eyes, ulcerated throat,
thickened lower portion of the esophagus and contracted stomach.
C-Inhalation:
Inhalation of acid fumes causes coughing, chocking and variable symptoms of
headache, dizziness and weakness followed by pulmonary edema with tightness in the
chest, air hunger and cyanosis. Haemoptysis and shortness of breath may continue for
several weeks.
D-Eye contact:
2
Conjunctival edema and corneal destruction occur from even dilute acids in the eyes.
The symptoms are pain, tearing, and photophobia.
Treatment:
A . Skin-contact:
1. Remove acid by flooding with water for at least 15 minutes.
2. Do not use chemical antidotes. The heat liberated in the chemical reaction may
actually increase injury.
3. Treat damaged areas as for thermal burns.
B. Ingestion:
1. Do not use gastric lavage or emesis because of the risk of perforation.
2. Ingested acid must be diluted by drinking quantities of water, milk, or egg albumin.
3. Give morphine sulphate to relieve pain.
4. Treat asphyxia by maintaining an adequate airway.
5. Treat shock by transfusion and by the administration of 5% dextrose in saline.
6. If symptoms are severe and perforation of the stomach or esophagus is suspected,
don’t give any oral remedy.
7. Maintain nutrition by giving 400 g of carbohydrate IV daily.
8. Give prednisolone to reduce esophageal stricture formation.
D. Eye contact:
1. Dilute the acid by flooding affected area with quantities of water in shower or
fountain for at least 15 minutes. The eyelids must be held apart during washing.
2. Do not use chemical antidotes.
3. Eye burns require an immediate attention of an ophthalmologist. If an
ophthalmologist is not available, wash the eyes and apply sterile bandages without
any medication. Pain is relieved by the systemic administration of analgesics. Then
take the patient to an ophthalmologist.
3
EXPERIMENT I:
Effect of conc. Sulphuric Acid on the Mucosa of Isolated Stomach or Intestine:
TOXICOLOGICAL ANALYSISScheme for volatile poisons:
Poison Name of Tests Results
1-Ethanol
2 -Methanol
3 -Cyanide
4 -Phenol
5 -Aniline
6 -Chloroform
TOXICOLOGICAL ANALYSIS
40
LAB No. 7 DATE………………
II- NON VOLATILE POISONSNON-VOLATILE ACIDIC & NEUTRAL POISONS : Procedure for extraction:The acidic residue of the previous experiment is to be extracted as follows:
1 .Extract twice with 10 ml portions of ether in a separating funnel.
2 .Extract twice with 10 ml portions of chloroform.
3 .Evaporate the combined organic extract on water bath (never use a flame in this experiment).
4 .Test in the resulting residue for non-volatile neutral and acidic poisons.
Chemical tests for individual poisons : Test for salicylates ; FeCl3 test:
-1 ml distillate + few drop FeCl3 (10 %) => violet color will develop.
Test for chlorpromazine (CPZ) : -Take 1 ml of distillate.
-Add 6 drops of Conc. H2S04 + one drop of FeCl3 => lilac color
Test for Phenobarbital:
Sodium Nitrite test:-1 ml distillate + 2 ml Conc.H2S04+ few crystals of Na nitrite => golden yellow color will
develop.
NON VOLATILE BASIC POISONS
41
Procedure for extraction:The aqueous solution remaining after previous extraction is treated as follows:
1 .Take 5 ml and make alkaline with ammonia.
2 .Extract twice with 5 ml portions of chloroform.
3 .Evaporate the combine organic extract to dryness in water bath (never use a flame in this experiment).
4 .Test in the resulting residue for non-volatile basic poisons.
Chemical tests for individual poisons
Test for strychnine-Put few mg of residue + 2-3 drops of Conc. H2S04 in a porcelain slap.
-Add few crystals of potassium dichromate (K2Cr2O7) —> blue violet rays will be formed
without shaking.
Test for atropineVitali's test
-Put few mg of residue + few drops of Conc. HNO3 in a porcelain dish.
-Evaporate to dryness
-Cool and dissolve in acetone and add few drops of alcoholic KOH -> light purple color
will be formed changing to red.
Test for quinine Fluorescent test
-dilute H2S04 dissolves quinine giving blue fluorescent solution.
Test for caffeine Murexide test
Put few mg of residue + few drops of Conc.HCL in a porcelain dish. Add 0.1 g potassium
chlorate (KCl04) and evaporate to dryness on water bath. Moisten the residue with few
drops of ammonia. The residue will acquire a purple color which disappears upon addition
of fixed alkalie (NaOH).
42
KING ABDUL AZIZ UNIVERSITYFACULTY OF PHARMACY
PHARMACOLOGY & TOXICOLOGY DEPT.
LAB No. 7 DATE..…………………:
Student name: Sample number( )
TOXICOLOGICAL ANALYSIS
A-Scheme for non-volatile acidic & neutral poisons :
Poison Tests Results
1-Tests for salicylates: -FeCl3 test:
2-Test for chlorpromazine (CPZ):
3 -Test for phenobarbitone: -Sodium nitrite test:
Conclusion: The poison(s) present may be ..……………………………… :
………………………………… …………………………………
43
KING ABDUL AZIZ UNIVERSITYFACULTY OF PHARMACY
PHARMACOLOGY & TOXICOLOGY DEPT.
LAB No. 7 DATE..………………………:
Student name: Sample number( )
TOXICOLOGICAL ANALYSIS
B- Scheme for non-volatile basic poisons :
Poison Tests Results
1-Test for strychnine:
2-Test for atropine: -Vitali’s test
3-Tests for quinine: -Fluorescent test:
4 -Tests for caffeine: -Murexide test
Conclusion: The poison(s) present may be …………………………………
………………………………… …………………………………
44
HYPOXIA
Lab. No. 8 Date…………………… :
Definition:
Hypoxia is a decrease in oxygen supply to the body, leading to decrease in energy supply
especially for brain and heart. If hypoxia exceeds two minutes, this will lead to irreversible
cerebral damage.
Utilization of oxygen by tissues:
During inspiration, air reaches alveoli at which the partial pressure of oxygen in air is
higher than that in blood, so passive diffusion of oxygen will occur from air to blood.
Oxygen in blood is carried by hemoglobin which is able to combine with oxygen in the
Fe2+ state to give oxyhemoglobin. Now the partial pressure of oxygen in blood is higher
than that in tissues, so oxygen is picked up by cells where the respiratory chain in
mitochondria produces energy.
Symptoms of hypoxia:
Due to decreased oxygen supply, the threshold at which different centers of brain are
functioning will decrease. If this level is very low, symptoms of hypoxia starts to appear:
Excitation in the form of tremors, convulsions, increased respiratory and heart rate. This is
followed by exhaustion and depression in the form of decreased respiratory and heart
rate, coma and finally death.
Causes of hypoxia:
Hypoxia may occur at different levels:
1. Defect in the air level due to reduced oxygen tension (concentration) in the air as in
case of high altitudes and badly aerated rooms.
2. Defect at the bronchi level due to obstruction in air airway passage as in case of:
a) Presence of mucous
b) Bronchoconstriction (histamine)
c) Corrosion of trachea
45
3. Defect in the mechanical process of respiration due to paralysis of respiratory
muscles (e.g. skeletal muscle relaxants like D-tubocurarine, and CNS depressants
like barbiturates and morphine).
4. Defect at the lung level due to pulmonary edema or pneumonia, the higher amount
of fluid will decrease surface area of alveoli leading to decrease in amount of air
exchanged, oxygen supply and decrease in amount of energy produced.
5. Defect in the oxygen-carrying capacity of blood due to:
a) Decrease in content of hemoglobin (as in case of anemia and hemorrhage).
b) Change in the nature of hemoglobin (as in case of Met-Hb, Sulf-Hb and Co-
Hb).
6. Tissue hypoxia or cytotoxic hypoxia due to defect in oxygen utilization by tissues
(as in case of cyanide poisoning in which cyanide combines with ferric ion,
cytochrome oxidase, so impairs its ability to carry oxygen.
7. Defect at glucose level (as in case of severe hypoglycemia) that is metabolic
hypoxia in which decrease in ATP energy production occurs.
Cyanide toxicity as an example of tissue hypoxia
Sources of cyanide:
Industry of rubber
Fertilizers
Crushed seeds of almonds and apricot
Mode of action:
Cyanide combines with cytochrome oxidase in the Fe3+ state, resulting in blocking its
ability to carry oxygen.
Symptoms:
Headache
Nausea, vomiting
Ataxia
Palpitation
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Convulsions
Coma and death
Cyanide kits for prophylaxis:
Sodium nitrite or amyl nitrite is used in addition to sodium thiosulfate.
EXPERIMENT :
1. Record the normal characteristics of a mouse and inject it intraperitoneally with
potassium cyanide in a dose of 7.5 mg/kg (conc. 0.25 %).
2. Record the onset time and note the signs of toxicity especially respiration, size of
pupil, cyanosis and convulsions.
3. Inject another mouse with 20 mg/kg (conc. 1%) of sodium nitrite intraperitoneally,
after 30 minutes inject the specified dose of potassium cyanide intraperitoneally.
4. Record the survival time and comment on the results.
5. Inject another mouse with 20 mg/kg of sodium nitrite intraperitoneally, & 0.2ml 0f
sodium thiosulphate wait 30 minutes then inject the specified dose of potassium
cyanide intraperitoneally.
6. Record the survival time and comment on the results.
47
KING ABDUL AZIZ UNIVERSITYFACULTY OF PHARMACYPHARMACOLOGY DEPT.
LAB No.8 DATE……………………:
Animal recording Sheet
DrugAntidote
)Na Nitrite(
Antidote mixture )Na Nitrite+ Na
thiosulphate(
Animal providedSex of animal
Weight of the animal
Concentration
DoseTime of injection
Inject the both provided mice with Drug and Drug+ Antidode then fill the following table
DrugDrug + antidote
)Na Nitrite(
Drug +Antidote mixture
)Na Nitrite+ Na thiosulphate(
Symptoms &
observation
Comment:
48
King Abdul-Aziz UniversityFaculty o Pharmacy
Dept. Of Pharmacology
49
KING ABDUL AZIZ UNIVERSITYFACULTY OF PHARMACY
PHARMACOLOGY & TOXICOLOGY DEPT.
Case 1
Acetaminophen (Paracetamol)Date………………… :
A 16-year-old white female weighing 43 Kg had ingested 25 tablets of acetaminophen
each containing 500 mg. Four hours after the ingestion, she went to an emergency room.
She claimed to have taken her oral contraceptive pill that morning and denied recent
exposure to other drugs. This anxious patient denied any discomfort, nausea, vomiting or
right upper quadrant abdominal pain. Physical examination revealed a well-nourished
female in no apparent distress. Her vital signs were blood pressure 124/60 mmHg, pulse
112/min., and irregular respiration 16/min., and temperature 370C. Results of examination
of the head, eyes, ears, nose and throat were normal. The lungs were clear and the heart
was not enlarged. No murmur or gallops were detected upon auscultation, but the patient
appeared to have sinus tachycardia. Normal bowel sounds were heard in the abdominal
examination. The liver spanned approximately 8 cm and was mildly tender to palpitation.
Extremities were normal in appearance without petechiae or purpura. Cranial nerves were
grossly intact and no abnormal reflexes were elicited.
Questions : 1. Toxic doses of acetaminophen may cause the followings
50
a- Murmur
b- Hypertension
c- Tenderness of the liver
d- Tachycardia
2. The following are true regarding the toxicity of acetaminophena- Diaphoresis usually occurs after 24 hours of ingestion
b- Serum concentrations of hepatic enzymes begin to rise 24 hours after ingestion
c- Jaundice maybe noted 3 days after ingestion
d- Pericarditis maybe noted during the second phase of toxicity
3. Regarding the metabolism of acetaminophen, the following are truea- The majority of acetaminophen is conjugated with sulphate
b- A part amounting to 2% of the administered drug is metabolized by P-450 enzyme
system
c- Reactive metabolite forms hippuric acid when it reacts with Glutathione
d- With an acute toxic doses, the first agent to be depleted is glucuronic acid
4. Determination of prothrombin time in patients poisoned with acetaminophen shows a- No change
b- Only a little change
c- Elevated early and progressively
d- Slightly elevated and without significance
5. The reactive metabolite of acetaminophen reduces the amount of a- Glutamate transferase
b- Glutathione
c- Hepatic cytochromes
d- Methionine
6. The specific antidote for acetaminophen is a- Cortisone
b- Phenobarbitone
c- Glutathione
d- Cysteamine
e- Penicillamine
7. Precursors of glutathione includea- Cysteamine
51
b- Methionine
c- Cysteine
d- N-acetylcysteine
8. he following agents reduce acetaminophen-induced toxicitya- Barbiturates
b- Alcohol
c- Glutathione
d- Methionine
9. The following are true regarding assessment of the severity of acetaminophen toxicity
a- 2 g can induce hepatotoxicity
b- 10 g could cause hepatic coma
c- Hepatic coma is possible when the half-life of the drug exceeds 15 hours
d- Generally, hepatotoxicity maybe induced by acetaminophen when its half-life is 5
hours or more
10. Give the meaning of each of the following terms:a-Murmur b-Petechiae
c-Gallops d-Purpura
e-Auscultation f-Hepatic encephalopathy
g-Palpitation h-Pericarditis
i-Myocardial necrosis
Case 2
52
Salicylates
Date………………… :
A 10 –year old female developed symptoms of an upper respiratory tract infection
with a temperature of 38.4 ºC, nasal congestion and general malaise. The child's mother
began treatment with two adult aspirin tablets (325 mg each) every 4-6 hrs. In addition,
the child was given one Coricidin "D" (chlorpheniramine maleate, aspirin (325 mg),
phenyl-propanolamine HC1 tablet every 4-6 hrs for nasal congestion. On the following
day, the child developed abnormal breathing with nausea and vomiting. The patient's
mother administered bismuth subsalicylate 1 tablespoonful (130 mg) every 4-6 hrs, for the
nausea, and vomiting. The patient continued to receive these drugs regularly until the
day of admission. On examination by the family physician, the patient was noted to be
hyperthermic, tachypneic, lethargic and disoriented with regard to time and place.
Physical examination on admission revealed an ataxic, hyperpneic and disoriented child
with a rectal temperature of 40ºC In addition, convulsions; coma, hyperglycaemia
(followed by hypo-glycaemia) and metabolic acidosis have been reported. The clinical
course progressed to pulmonary oedema, haemorrhage, renal failure and oliguria.
Questions :
53
1 (Nomogram is used to estimate: a- Median lethal dose of aspirin
b- Toxic dose of aspirin
c- The severity of acute salicylate poisoning
d- Whether the toxicity is mild, moderate or severe
2 (Toxic effects of aspirin are produced when: a- a dose of 100 mg/kg is given
b- a dose of 150 mg/kg is given
c- a serum level of 60 mg/100 ml is monitored
d- a serum level of 30 mg/100 ml is monitored
3 (Respiratory alkalosis is induced by salicylates is due to
a- Increased accumulation of CO2
b- Increased accumulation of 02
c- Inhibition of Krebs cycle dehydrogenase
d- Uncoupling of oxidative phosphorylation .
4 (Uncoupling oxidative phosphorylation enhances the formation of
a- Oxaloacetic acid
b- Glutamic acid
c- Acetic acid
d- Lactic acid
5 (Severe disturbances in glucose metabolism induced by aspirin are due to a- increased blood insulin
b- increased release of insulin
c- inhibition of glycogenolysis
d- increased aerobic metabolism of glucose
6 (Toxic effects of aspirin are also seen in blood coagulation mechanism and consist of:
a- reduced plasma prothrombin
b- increased prothrombin time
c- stimulation of platelet aggregation
d- reducing the formation of TXA2
7 (Chronic salicylism:
54
a- May occur at level of 70-90 mg%
b- The patient suffers from fever, dehydration, abnormal bleeding parameters .
c- Mortality rate is very low.
d- It mostly occurs in elderly people
8 (Rapid testing for salicylate presence can be done by: a-adding ammonium hydroxide to urine
b-adding ferric chloride to acidified & boiled urine.
c-phenistix reagent strip to urine.
d-adding sulfuric acid to urine.
9 (When patient with acute intoxication is first seen, what studies are essential in addition to serum salicylate?
a-Blood glucose.
b-CSF glucose
c-Blood & urine pH
d-Urine specific gravity.
10 (Gastric emptying: a-Should be attempted up to 12 hours postingestion.
b-Is not beneficial after 6 hours.
c-Is only effective in the first 4 hours
d-Is ineffective in treatment of salicylate intoxication
11 (The best technique for treating salicylate intoxication is: a-Hemodialysis
b-Gastric dialysis
c-Resin Hemoperfusion
d-Charcoal Hemoperfusion
Case 355
OPIATESDate………………… :
One- year-old boy is brought via ambulance to the ER in an unresponsive state. The
emergency medical technician who came with the child told the attending physician that
the child was only lethargic when he was initially reached by them, becoming
unresponsive shortly before arrival. His mother gives the history that he was playing with
his aunt's purse containing a bottle of propoxyphen hydrochloride capsules, 32mg each.
It is estimated that he took between 5 and 10 tablets. The ingestion is felt to have
occurred 30 minutes prior to arriving to ER.
Questions : (1Which of the following is the correct early management of this case:
a-1.Lavage with mineral or olive oil.
2.Give analeptic drug.
3.Maintaine airway.
b-1.Establish airway by artificial respiration.
2 .Evaluate vital signs and neurologic status as rapid as possible.
3.Give antidote.
c-1. Do a careful neurologic examination.
2 .Maintain stable vital signs .
3 .Establish airway.
d-1.Establish airway.
2 .Quickly evaluate status of patient including vital signs.
3.Give analeptic drug.
2)The specific drug to counteract effects is :
a-Naloxone
b-Caffeine sodium benzoate
c-Methadone
d-Amphetamine
3) There was a good response to this; however, it was felt necessary to empty the
stomach. For this child, this was accomplished:
56
a-Mineral or olive lavage
b-Normal saline followed by activated charcoal
c-Normal saline only
d-Sodium sulphate solution
This procedure was accomplished successfully and child was admitted to the ICU
and continued to the antidote apprpiatly
4) It was noted that he should be carefully observed and followed for:
a-Renal failure
b-Convulsions
c-Pulmonary edema
d-Hyperglycemia
5) The patient continued stable and it was felt that the antagonist was no longer needed.
The other therapy used was:
a-Alkalinaztion of urine
b-Forced diuresis
c-Dialysis
d-Symptomatic only
By 24h after ingestion, the child was alert and able to feed himself with his own
bottle. Recovery was felt to be complete and rapid. Hospitalized remained
hospitalized one more day. It was discovered at tjis time that the child's aunt was
pregnant. She was advised not to take this drug?
6)Why should she not to take this drug:
a-Newborn infants experience withdrawal syndrome
b-Newborn have a high risk of hyperbilirubinemia
c-It increases chance of premature birth
d-It may be teratogenic
7) Irregular breathing produced by toxic doses of opiods may be related to:
a-Decrease in responsiveness of respiratory centers to CO2
b- Increase in responsiveness of respiratory centers to CO2
c- Stimulation of the medullary centers.
d- Inhibition of the medullary centers
8) The following are among Pharmacological actions of narcotic analgesics:
a-Increasing propulsive movement of intestine
57
b-Decreasing the vagal activity of GIT
c-Increasing the resting tone of the smooth muscle of the large intestine
9) Narcotic detoxification can be produced by the following :
a-Methadone
b-Naloxone
c-LAAM
d-Physostigmine
10) The following disorders are among complications of narcotic analgesics toxicity:
a-Nephrotic syndrome
b-Viral hepatitis A
c-Viral hepatitis B
d-Intestinal bleeding
Case 4
58
DIGOXINDate………………… :
A 20-month-old child weighing 11.4 Kg was found by his grandmother with an open bottle
of her “heart medicine”. There were no tablets in his mouth at the time, although several
tablets were moist, and many were spread around the room. The heart pills were
identified as digoxin, 0.25 mg.
Approximately one hour later, the child became sick and vomited several times. The
grandmother at this time mentioned the events to the parents who had not been home
when the accident occurred. They phoned the Poison Control Center to determine the
relationship between the illness of the child and events of the previous hour. The parents
were instructed to use syrup of ipecac and were told to bring the child to the emergency
room.
Physical examination on arrival at the emergency room revealed a well-developed child
who was having dry vomiting and who was pale but alert. His vital signs were blood
pressure 98/54 mmHg, pulse 60/min. and irregular respiration 28/min. and temperature
370C. Upon examination, the head, eyes, ears, mouth, nose, neck and chest were all
normal.
An ECG showed first degree AV block and occasional supraventricular extrasystole. The
abdominal examination showed a soft abdomen with active bowel sounds and no
organomegaly. Skin, joints were all normal with no petechiae, ecchymoses, and rashes or
swelling. The neurology evaluation showed slight decreased deep tendon reflexes. The
chest X-ray examination, urine analysis and hematological values were all within normal
limits. The initial digoxin blood level was reported as 12µg/ml taken at 3.5 hours after
ingestion.
Questions:
59
1) The early symptoms of digoxin intoxication area. Persistent nausea and vomiting
b. Anorexia
c. Convulsions
d. Drowsiness especially in children
e. Abdominal colic
2) Drug management of the digoxin poisoned patient depends on the arrhythmia present so that various regimens of drug are necessary. The following are the most useful
a. Phenytoin
b. Quinidine
c. Procainamide
d. Lidocaine
3) The electrolyte used to prevent arrhythmia is a. Calcium
b. Sodium
c. Potassium
d. Magnesium
4) Other treatment which may be necessary a. Diazepam for CNS effects
b. Hemodialysis
c. Diuretics
d. Antiemetics
5) Mechanisms of digoxin-induced toxicity include a. Inhibition of vagal nerve activity
b. Inhibition of Na+-K+ ATPase pump
c. Stimulation of CTZ
d. Stimulation of heat regulatory center
6) The reported lethal dose for adultsa. 70µg/ml
b. 80µg/ml
c. 15 mg/kg
d. None of these
7) The following are true regarding the treatment of digoxin toxicity
60
a. Glucose and insulin are given to decrease extracellular level of potassium
b. Digitalis-specific antibodies are useful in overcoming poisoning
c. Phenytoin sodium is given at a dose of 40 mg I.V.
d. Atropine sulphate reverses the increased vagal tone on the S-A node and to
correct sinus rhythm
8) Overdosages of digoxin may cause the following electrolyte imbalancea. Alkalosis
b. Hypomagnesaemia
c. Hyponatremia
d. Hyperkalemia
9) The following symptoms are not included among those produced by digoxin toxicity
a. Hypertension
b. Visual disturbances
c. Loss of appetite
d. Skin rash
10)Give the meaning of each of the following termsa- Organomegaly e- Anorexia
b- Petechiae f- Amblyopia
c- Ecchymoses g- Blurred vision
d- Delirium
Case 561
CYANIDEDate………………… :
Wilfred S. was brought to the ER of his community hospital by his coworkers with the
history of having approximately ten minutes earlier drunk a glass of cold water from a
several-quart, large-mouth glass jar which had been in the refrigerator of a house that his
exterminating firm had just fumigated within the last 24 hours with hydrogen cyanide gas.
The house had just been opened and the gas-tight envelope was just being removed
when he entered the house wearing his protective mask and brought from the house the
jar of cold water. He took it outside of the house, removed his mask and poured a glass of
cold water. A colleague was about to drink some of the same water when the patient
warned him that the water “had a funny burning taste”. This associate tasted the water on
the tip of the tongue and agreed. As he was doing this, the patient said, “Take me to
hospital” as he suddenly collapsed into unconsciousness. The time had been 3 to 5
minutes. The hospital was 5 minutes away, but the treating physician was immediately
available upon arrival. The patient was unresponsive with shallow, irregular, grasping
respirations with a bradycardic pulse of poor quality and blood pressure of 100/50. There
was cyanosis.
62
Questions:1. The mechanism of action of the cyanide ion resulting in toxicity is due to its
a-reaction with the ferrocholinate in the mitochondria
b-reaction with ferric ion of the cytochrome oxidase in mitochondria
c-reaction with the ferrous ion of the cytochrome oxidase in mitochondria
d-reaction with acetylcholine at the chemoreceptor cells
2. At low concentrations cyanide directly a-depresses the respiratory center at the level of pons
b-stimulates the chemoreceptor sod the medullary respiratory center
c-blocks oxidative metabolism of the chemoreceptors of the aortic and carotid
bodies
d-inhibits the glycolytic pathway
3. The following are truea-the cyanide ion is easily absorbed by inhalation or ingestion resulting in severe
toxicity and death in minutes to three hours
b-cyanide cannot be absorbed through the skin
c-there are no natural mechanisms for the body to detoxify or to excrete cyanide
d-little is known regarding lethal dose and almost any dose can be fatal
4. The immediate recognition of cyanide poisoning is crucial since thaerapy must be started immediately. The patient realized what had happened because a-Hydrocyanic acid in concentrations as low as 1 ppm emits a characteristic odor
of bitter almonds or macaroons
b-The odor is that of garlic
c-The taste of the acid and the sodium and potassium salts is that of garlic
d-Only the odor is characteristic
This recognition probably saved the life of the patient's colleague. It certainly alerted the
patient.Because cyanide is one of the most rapidly acting and toxic of all poisons,
immediate therapy is essential. The co-worker mentions that a cyanide antidote kit is in a
truck still located at the house. He is sent to bring this to the hospital as the appropriate
antidote is not available at this small hospital.
5. In the interim the treatment is
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a-Lavage b-nothing is possible
c-Dopamine d-100% oxygen
The patient was given this therapy, although his respirations worsened and he became
more cyanotic. Positive pressure oxygen was necessary.
6. He was put on a cardiac monitor which revealed a-lengthening of QT interval b-pronounced ST elevation
c-abnormal QRS d-depressed T wave
The specific antidote is delivered. The time between ingestion and arrival is now 30
minutes.
7. The kit was sealed with a wire and marked for physician use only. It contains a-spirits of ammonia b-amyl nitrite
c-sodium thiosulfate d-metaraminal
e-sodium nitrite
8. Other antidotes if the kit was unavailable to slow toxicity area-activated charcoal b-none for PO or inhalation route
c-aluminium hydroxide PO to slow absorption d-oral nitrates
The kit was immediately opened and amyl nitrite inhalation under the oxygen mask was
given while the sodium nitrite was put into the springs 10 cc of a 3% solution over 3
minutes, followed by 50 cc of a 25% aqueous solution of sodium thiosulfate, over 10
minutes. After it was given IV, there was definite improvement in the patient's cyanosis yet
he was not breathing spontaneously. BP 50/30. Inhalation nitrite was continued as was
oxygen and positive pressure.
9. The therapy results in a-high concentration of methemoglobin
b-competition between CN and cytochrome
c-dissociation of cytochrome
d-production of complex which will transport oxygen
10. This results ina-combination with cyanide complex
b-removal of ion preventing the formation of the toxic complex
c-competition with cytochrome oxidase for cyanide ion
d-decomposition of methemoglobin
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11. In addition to removal of cyanide by the lungs and some trapping mechanisms ,the body has one other natural mechanism for removal or detoxification
a-combination with glutathione b-reaction with rhodanese
c-reaction with glucokinase d-reaction with succinylcholase
12.This nontoxic substance is a-readily excreted by the urine b-excreted through the bile
c-slowly excreted in the urine d-exhaled
Following the use of the three antidotes, there was definite improvement in his color, but
there were no spontaneous respiration and BP was 50/30. There was no change in EKG
and pulse continued weak. Oxygen was continued at 100% under pressure. Twenty
minutes after specific antidote he developed spontaneous respirations with rise in BP and
pulse. He continued to have the bluish color of methemoglobin. Additional thiosulfate was
given as well as one unit of whole blood. Following this, he responded to stimuli and had
normal papillary reaction. He continued cyanotic however, this was expected in view of
the methomglobinemia. A repeat dose of 10 cc sodium nitrite 3% and thiosulfate is given
slowly over 10 minutes.
13. The question of the danger of methemoglobin is raised. A local Poison Control Center was called as the patient had been receiving 50 cc of a 25% sodium thiosulfate given slowly. They responded that
a-10 cc of the nitrite is too much of a second dose
b-methomglobinemia cannot be detected by skin color until 30%, although
symptoms do not occur until 65%
c-follow the methemoglobin levels, keeping the level below 50%
d-since cyanosis from methemoglobin of 15% is readily obvious, only way to
judge therapy is blood assay
e-hemoglobin can be released spontaneously over a period of hours – do not
worry
14. If methemoglobin exceeds toxic level the antidote is a-ascorbic acid b-100% oxygen only
c- methylene blue d- packed red cells only
15.The nitrites may also result in a- profound fall in blood pressure b- anuria
c- hypertension d-convulsion
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16.The best treatment isa-furosemide b-paraldehyde
c- apresoline d-epinephrine or its cogenors
17.100% oxygen was used throughout treatment period. The role of oxygen in cyanide poisoning is
a-only effective at hyperbaric pressures
b-only effective as it potentiates the effects of the thiosulfate or nitrite-thiosulfate
combination
c-primarily protective for excessive methemoglobin production
d-not important
This was used with good results following the second dose of antidotes. After five hours of
stability of vital signs yet poor responsivenessand continued therapy, he suddenly
developed periods of apnea with irregular respirations and hypertension. The diagnosis of
acute pulmonary edema was made and therapy with diuretics, aminophylline, and
Cedilanid was started. With this treatment, his chest improved within 90 minutes. Over the
next several hours he became hypotensive, febrile, flaccid and required respiratative
measures. Despite appropriate supportive therapy with excellent response to aramine and
diuretics, his heart weakened and he was pronounced dead 28 hours after ingestion.
Despite the widespread belief that the ingestion of cyanide is invariably fatal, as long as
the heart beats the specific therapy is almost always effective. Although most cases of
cyanide poisonings are cases of suicides, work-related accidents can occur. Rarely are
children involved
18. The following is truea-The dose of sodium nitrite appropriate is less for children, as lethal
methomglobinemia may result
b-Methylene blue is always indicated
c-Exchange transfusion is treatment of choice
d-The treatment is the same
19. Sources of cyanide for children in the home cana-photograph developers b-instant adhesives
c-plants, especially while cherry seeds, hydrangea, apricot pits and chokecherry
d-rodenticides e-silver polishes
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20.A new antidote which can be used with thiosulfate to replace the nitrite is a-puruvic-cyanohydrin b-o-aminopropiophenone
c-cobalt nitrite d-hydroxycobalamine
21. It functions by a-producing methomoglobin more rapidly
b-combines with cyanide to form vitamin B12
c-stimulates the rhodanese enzyme
d-forms a complex readily oxidized by CO2
22. Which are true?a-chronic poisoning does not occur
b-pulmonary edema can result from chronic exposure
c-pathologically demyelinization in the brain results
d-changes in brain metabolites results
e-changes in brain metabolites result, with decreases in oxidative metabolism