THIRD PROBLEM

Disastrous Pills
FORTUNE DE AMOR
405140230
GROUP 8
 Metals and Metalloids
Metals : chemical elements that possess three general properties:
(1) they are a good conductor of heat and electricity,
(2) they are able to form cations,
(3) they can combine with nonmetals through ionic bonds.

 In clinical toxicology, the following metals, noted in ascending atomic weight, are
usually considered under the concept of “heavy” or “toxic” metal poisoning:
beryllium, vanadium, cadmium, barium, osmium, mercury, thallium, and lead,
with lead and mercury being the metals most clinically significant concerning
human poisoning.
 Metalloids : chemical elements with properties intermediate to those of metals
and nonmetals.
 Although there is no precise definition, metalloids tend to have these two general
properties:
(1) they are semiconductors of electricity, and
(2) they form amphoteric oxides.
 In order of ascending atomic weight, the following elements are generally
considered metalloids: boron, silicon, germanium, arsenic, antimony, tellurium,
and polonium; arsenic is the most clinically significant metalloid.
 Exposure to either metals or nonmetals can be from
(1) the pure element
(2) an organic compound containing the toxic element (defined as those
compounds that contain carbon), or
(3) an inorganic compound containing the element (defined as those that do not
contain carbon).
the metals and metalloids often present
with protean manifestations primarily
affecting five systems: neurologic,
cardiovascular, GI, hematologic, and
renal. Effects on the endocrine and
reproductive systems are less clinically
apparent.
It is important to recognize an initial
“index case” of metal poisoning to
prevent others from being poisoned
when the metal source is
environmental or industrial
 Metals and Metalloids: LEAD
PHARMACOLOGY
 Absorption of inorganic lead is usually via the respiratory and GI tracts; skin
absorption is negligible.
 Absorption of organic lead can occur after inhalation, ingestion, and dermal
exposure.
 Greater than 90% of the total body lead is stored in bone, where it easily
exchanges with the blood.
 Lead can be transferred across the placenta, a process exacerbated by increased
bone turnover during pregnancy.
 Excretion of lead occurs slowly; the biologic half-life of lead in bone has been
estimated to be 30 years.
PATHOPHYSIOLOGY
 In the CNS, the toxic effects of lead include
(1) injuries to astrocytes, with secondary damage to the microvasculature and
resultant disruption of the blood–brain barrier, cerebral edema, and increased
intracranial pressure;
(2) decreases in cyclic adenosine monophosphate and protein phosphorylation,
which contribute to memory and learning deficits;
(3) alteration with calcium homeostasis, which leads to spontaneous and
uncontrolled neurotransmitter release.
 In the peripheral nervous system, lead
causes primary segmental demyelination,
followed by secondary axonal
degeneration, mostly of the motor nerves.
 In the cardiovascular system, small but
statistically significant increases in the
prevalence of hypertension and
atherosclerotic vascular disease are found
in individuals with elevated blood lead
levels.
 In the hematopoietic system, lead
interferes with porphyrin metabolism,
which may contribute to lead-induced
anemia.
 In the kidney, lead affects the proximal tubule,
producing Fanconi’s syndrome with aminoaciduria,
glycosuria, phosphaturia, and renal tubular acidosis.
- Chronic interstitial nephritis and increased uric
acid levels are due to increased tubular
reabsorption of urate.
- Chronic lead toxicity has been linked to gout
and chronic renal failure.
 chronic lead exposure, increased calcium deposition
at growth plates may be seen as “lead lines” on
radiographs of long bones. Lead induced adverse
effects on the reproductive system include increased
fetal wastage, premature rupture of membranes,
depressed sperm counts, abnormal or nonmotile
sperm, and sterility.
DIAGNOSIS
 History  occupational or
environmental, related to recent travel
or immigration, a hobby, or a retained
lead bullet
 Toxicity due to retained lead bullets
may manifest several decades after
being shot.
 The combination of abdominal or
neurologic dysfunction with a
hemolysis should raise suspicion for
lead toxicity. Consider the diagnosis in
all children presenting with
encephalopathy.
 The definitive diagnosis  blood lead level ↑,
with or without symptoms.
The blood lead level at or >5 micrograms/dL (0.24
micromol/L) are considered elevated in children.
 fingerstick capillary blood (always should be
confirmed on a venous blood sample).
 Diagnostic studies focus on evaluation for
anemia and examination of radiographs for
evidence of lead exposure.
 abdominal radiographs  radiopaque material in
the GI tract.
 Radiographs of long bones (especially of the
knee) “lead lines”
 Metals and Metalloids : ARSENIC
 tasteless, odorless metalloid that causes significant acute and chronic toxicity worldwide
PHARMACOLOGY
 well absorbed by GI, respiratory, and parenteral routes and may be absorbed through
nonintact skin.
 pentavalent arsenic (arsenate)  water solubility  mucous membranes
 trivalent arsenic (arsenite)  lipid solubility  skin
 After absorption : localizes in erythrocytes and leukocytes or binds to serum proteins.
 Within 24 hours : redistribution into the liver, kidney, spleen, lung, GI tract, muscle, and
nervous tissues occurs, with subsequent integration into hair, nails, and bone.
 Elimination from the blood is rapid, and excretion is predominantly renal.
 Arsenic crosses the placenta  teratogenic
PATHOPHYSIOLOGY
Acute exposure  dilatation
and increased permeability
of small blood vessels  GI
mucosal and submucosal
inflammation and necrosis,
cerebral edema and
hemorrhage, myocardial
tissue destruction, and fatty
degeneration of the liver and
kidneys.
DIAGNOSIS
 acute arsenic poisoning should be considered in a patient with hypotension that was
preceded by severe gastroenteritis.
 abdominal radiograph  intestinal radiopaque metallic flecks
 ECG  prolonged QT interval (especially in subacute poisoning)
 CBC  normocytic, normochromic, or megaloblastic anemia, and/or a
thrombocytopenia.
 WBC count ↑ acute toxicity, ↓chronic toxicity
 Definitive diagnosis of acute poisoning : ↑ arsenic levels in a 24-hour urine collection
 Normal urinary arsenic level : below 50 micrograms/L (0.67 micromol/L)
total urinary arsenic excretion in an unexposed patient typically does not exceed 100
micrograms/d (1.3 micromol/d).
 If the baseline urinary level is within normal limits and arsenic intoxication is still
suspected, hair and nail clippings should be harvested for laboratory analysis.
differential diagnosis
 septic shock, encephalopathy, peripheral neuropathy (including Guillain-Barre
syndrome), Addison’s disease, hypo- and hyperthyroidism, patients with the
previously mentioned dermatologic manifestations, Korsakoff’s syndrome,
persistent gastroenteritis and/or cholera-like diarrhea, porphyria
 Other metal toxicities such as thallium and mercury, and unexplained, prolonged
malaise and weakness.
TREATMENT
 first taskstabilize circulatory function
(hypotension and dysrhythmias are the chief causes
of death)
 Hypotension  crystalloid volume replacement,
vasopressor (dopamine, norepinephrin)
 Ventricular tachycardia and fibrillation lidocaine,
amiodarone, and electrical defibrillation as
necessary.
 torsade de pointes  Magnesium sulfate,
isoproterenol
 Drugs that prolong the QT interval that should be
avoided  classes IA (procainamide, quinidine, and
disopyramide), IC, and III antidysrhythmics
 Potassium, calcium, and
magnesium levels should be
monitored
 Wholebowel irrigation 
intestinal radiopaque materials
consistent with arsenic.
 Seizures  benzodiazepines and
general anesthesia as necessary.
 In cases of suspected homicidal
intent, patients should be advised
to avoid food and drinks prepared
by others, and visitor contact with
hospitalized patients should be
monitored carefully.
 Treat patients with acute arsenical
poisoning or severe, life-threatening
toxicity with dimercaprol until the
clinical condition stabilizes and
succimer, the less toxic oral chelating
agent, can be substituted.
 Do not delay chelation in severely ill
patients until laboratory confirmation
because chelation is most effective
when given within minutes to hours of
exposure
DISPOSITION AND FOLLOW-UP
Hospitalization is recommended for
(1) patients with acute or
lifethreatening known or suspected
arsenic poisoning
(2) chronically poisoned patients
requiring dimercaprol therapy
(3) patients in whom suicidal or
homicidal intent is suspected.
 Metals and Metalloids : MERCURY
PHARMACOLOGY
 Elemental mercury is
absorbed primarily by vapor
inhalation.
 Inorganic mercury salts are
absorbed primarily through
the GI tract, but they may also
be absorbed across intact skin.
 Organic mercury compounds
are also primarily absorbed by
the GI tract.
CLINICAL FEATURES
 Elemental Mercury : shortness of breath,
fever/chills, cough, nausea, vomiting, diarrhea,
metallic taste, headaches, weakness, and blurry
vision.
 Inorganic Mercury :
GI: metallic taste, burning sensation in the
mouth, loose teeth, mucosal lesions and
fissures, excessive salivation, and nausea.
Neurologic: tremor, neurasthenia, and erethism.
Acrodynia
 Organic Mercury :
orofacial paresthesias
are a common initial
symptom, followed
by headache, tremor,
and fatigue.
In severe cases,
patients may develop
ataxia, muscle
rigidity and
spasticity, blindness,
hearing deficits, and
dementia.
 Carbon Monoxide Poisoning
The most common cause are from Sign and symptoms :
 Motor vehicle exhaust  Headache
 Smoke from fires  Dizziness
 Engine fumes  Nausea and vomiting
 Nonelectric heaters  Fatigue
 Confusion, depression & Hallucinations
 Drowsiness
 Visual changes
 Fainting
 Seizure
 Carbon Monoxide Poisoning
Treatment
Complications
 High-dose oxygen until
o Impaired intellectual function
asymptomatic + HbCO
<10% o Short-term memory loss
 HbCO more than 40% o Dementia
> hyperbaric pressure > o Amnesia
provide even higher o Psychosis
doses of oxygen o Irritability
Prognosis o Speech disorders
 Death can result from severe cases even o Parkinson disease
with proper treatment > long-term brain o Cortical blindness
damage>severe memory loss, difficulty o Depression
thinking, or other neurologic or
psychiatric problems
 Kerosene Intoxication
contain only hydrogen and carbon • HEART AND BLOOD
Signs and symptoms – Low blood pressure -- develops rapidly
• AIRWAYS AND LUNGS • NERVOUS SYSTEM
– Breathing difficulty (from inhalation) – Convulsions
– Throat swelling (may also cause breathing – Depression
difficulty) – Dizziness
• EYES, EARS, NOSE, AND THROAT – Drowsiness
– Pain – Euphoria ("drunk" feeling)
– Vision loss – Headache
• STOMACH AND INTESTINES – Loss of alertness (unconsciousness)
– Abdominal pain – Seizures
– Bloody stools – Weakness
– Burns of the esophagus (food pipe) • SKIN
• Vomiting, possibly with blood – Burns
– Irritation
 Kerosene Intoxication
Prognosis
• The faster a person gets medical help, the better the chance for recovery
Complications
• Swallowing kerosene > damage to the linings of the mouth, throat, esophagus
(food pipe), stomach, and intestines
• Kerosene gets into the lungs (aspiration) > permanent lung damage
ORGANOPHOSPHATES
ORGANOPHOSPHATES
Intoksikasi Obat
 Acetaminophen
 Acute ingestion of more than 150–200 mg/kg (children) or 7 g total (adults)
 highly toxic metabolite is produced in the liver

 Manifestations :
 Asymptomatic, mild gastrointestinal upset (nausea, vomiting)
 elevated aminotransferase levels and hypoprothrombinemia (24–36 hours)
 fulminant liver failure occurs  hepatic encephalopathy and death
 Renal failure may also occur

Katzung BG, Masters SB, Trevor AJ, Basic Clinical

Pharmacology. 11th edition. US: McGraw-Hill, 2007
 Treatment
Liver transplantation for patients with fulminant hepatic failure
Antidote acetylcysteine
 glutathione substitute  binding the toxic metabolite as it is produced
 most effective when given early and should be started within 8–10 hours if
possible

Katzung BG, Masters SB, Trevor AJ, Basic Clinical

Pharmacology. 11th edition. US: McGraw-Hill, 2007
Acetaminophen
 Acetaminophen Intoxication
• Serum acetaminophen concentration
 Determine the need for
antidotal therapy for acute
intoxication:

• >150 µg/mL at 4 hours

• Reduced to 4,7 µg/mL at
24 hours

Rosen’s emergency medicine. 8th ed..

 Acetaminophen Intoxication
Chronic ingestion
• Determining whether the patient
is at risk for hepatotoxicity

• Evaluating the patient by

measuring a serum
acetaminophen concentration &
AST

• Initiating therapy with NAC, if:

– AST >50 IU/L
– AST < 50 IU/L, but serum
acetaminophen ↑↑

Rosen’s emergency medicine. 8th ed..

 Acetaminophen Intoxication
N-Acetylcysteine  should not be delayed > 8 hours

Rosen’s emergency medicine. 8th ed..

 Benzodiazepine Toxicity
High doses of benzodiazepines can produce more serious side effects.
Signs and symptoms of acute toxicity or overdose may include the
following:
 Dizziness
 Confusion
 Drowsiness
 Blurred vision
 Unresponsiveness
 Anxiety
 Agitation

http://emedicine.medscape.com/article/813255-overview
Prehospital care for patients who have overdosed on
benzodiazepines (BZDs) includes the following:
Cardiac monitoring
Supplemental oxygen and airway support
Intravenous (IV) access
Rapid glucose determination (finger stick) and administration
of D50 if necessary

http://www.webmd.com/mental-health/addiction/benzodiazepine-abuse
 Treatment
Flumazenil is a competitive BZD receptor antagonist
Adverse events: agitation and gastrointestinal symptoms,
serious adverse events include supraventricular arrhythmia and
convulsions
Contraindication: seizure, head injury

http://emedicine.medscape.com/article/813255-treatment#d11
 Digoxin Intoxication

Clinical features
May be asymptomatic
May produce dysrhythmias or
conduction block
Non-cardiac symptoms

Diagnosis
Serum digoxin level (steady-state
serum), in 6-8 hrs
Rosen’s emergency medicine. 8th ed..
 Management
 Digoxin-specific Fab (DigiFab)
– In life threatening dysrhythmias:
 10 vials (acute ingestion), administer
within 30 mins
 4-6 vials (chronic ingestion)
 20 vials (in cardiac arrest)
– Based on the amount ingested, or
– Based on serum digoxin concentration
 Electrolyte correction
– Maintenance of serum potassium level
 Atropine 1 mg IV (adults) for severe bradycardia & AV
block
 Phenytoin & lidocain
Rosen’s emergency medicine. 8th ed..
 Opioid
Toxicity occurs as a result of intentional overdose, intentional
abuse, or adverse effect of therapeutic use
Sign and symptom:
Altered mental status, such as confusion or delirium
Breathing problems. Breathing may slow and eventually stop.
Extreme sleepiness or loss of alertness
Nausea and vomiting
Small pupils

https://medlineplus.gov/ency/article/000948.htm
Opioid
 Opioid

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=hssamhsatip&part=A48606&rendertype=
table&id=A49321
 Treatment

Breathing support, including oxygen,

or a tube that goes through the mouth
into the lungs and attachment to a
breathing machine
Intravenous (IV, through a vein) fluids
Medicine called naloxone (Evzio,
Narcan) to block the effect of the
opioid on the central nervous system
(such medicine is called a narcotic
antagonist)

https://medlineplus.gov/ency/article/000948.htm