2. Medical Toxicants
Drugs are biologically active molecules
used in the
treatment,
prevention &
diagnosis of disease.
However, drugs have made & will continue
to make a major contribution to human health,
we must accept the risks attached to these
benefit.
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Medical Toxicants
3. Medical Toxicants cont’d,...
The basic mechanisms for the toxicities arising
from drugs are
Direct & predictable toxic effects due to over
doses.
Toxic effects occurring after repeated therapeutic
doses.
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Medical Toxicants
4. Medical Toxicants cont’d,...
Direct but unpredictable toxic effects occurring
after single therapeutic doses due to idiosyncratic
response (peculiar response of an individual to a
drug).
Toxic effects due to another drug or substance
interfering with the disposition or pharmacological
response.
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Medical Toxicants
5. Acetaminophen is analgesics
for mild &moderate pain
which is very safe provided only the normal
therapeutic dose.
Acetaminophen is one of the drugs most
commonly involved in
suicide and accidental poisoning.
Initial symptoms after an overdose are mild
and non specific,
often resulting in delayed arrival for medical care
or a missed diagnosis.
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Medical Toxicants
6. Acetaminophen cont’d,...
Acute ingestion of more than
150-200mg/kg (children) or
7gm (adults) is considered potentially toxic.
Paracetamol is metabolized
mainly by conjugation &
minor proportion metabolized by oxidation.
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Medical Toxicants
7. Acetaminophen cont’d,...
However, overdoses change the metabolic
scheme giving a rise in toxic metabolite which
react with liver proteins &
cause tissue damage (leading to hepatic toxicity).
Initially, the victim is
asymptomatic or has mild GI upset (nausea,
vomiting) which
followed by evidence of liver injury.
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Medical Toxicants
8. Acetaminophen cont’d,...
Treatment
GI decontamination
Activated charcoal is beneficial within 1 to 2 h
post ingestion.
At 8 h postingestion, activated charcoal, emetics, or
gastric lavage are not necessary.
An acetaminophen level obtained 4 h later
determines follow-up treatment with an
antidote(acetylcysteine).
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Medical Toxicants
9. Acetylsalicylic acid, commonly known as
aspirin,
is still one of the most widely used minor
analgesics.
Salicylate poisoning is a much less common
cause of childhood poisoning deaths since
the introduction of child-resistant container and
the reduced use of baby aspirin.
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Medical Toxicants
10. Aspirin cont’d,...
Salicylates, however still accounts for
numerous suicidal and accidental poisonings.
Salicylate Poisoning can also result from
chronic over medication;
this occurs most commonly in elderly victims
using salicylates for chronic pain
because of impaired biotransformation, excretion &
others.
Salicylic acid is then metabolized by
conjugation.
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Medical Toxicants
11. Aspirin cont’d,...
These conjugation steps are saturable
so the half life of aspirin increases significantly
with only small increase in the number of tablets.
The first sign of salicylate toxicity is often
hyperventilation and
respiratory alkalosis due to medullary stimulation.
Metabolic acidosis follows
due to accumulation of intracellular lactate as well
as excretion of bicarbonate by the kidney.
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Medical Toxicants
12. Aspirin cont’d,...
Treatment
GI decontamination
Within the initial presentation the use of gastric
decontamination (activated charcoal) has shown
to reduce the amount of active salicylate by 50-
80%.
Fluid replacement is very important in the
management of salicylate toxicity
Toxicity can induce major fluid losses
through tachypnea, vomiting, hypermetabolic
state, and insensible perspiration.
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Medical Toxicants
13. Aspirin cont’d,...
The most important management is through
urine alkaliniztion
Alkalinization with NaHCO3 results in
enhanced excretion of ionized acid form of
salicylate
Hemodialysis
These are indicated in specific situations due
to the ability to remove salicylates as well as
correct fluid, electrolyte, and acid-base
disorders.
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Medical Toxicants
14. Aspirin cont’d,...
Absolute Indications for Hemodialysis
Renal failure
CHF
Acute lung injury
Persistent CNS disturbances
Progressive deterioration in vital signs
Severe acid-base or electrolyte imbalance, despite
appropriate treatment
Hepatic compromise with coagulopathy
Salicylate concentration (acute) > 100 mg/dL (in
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Medical Toxicants
15. Sedative-hypnotics can cause dose-related
depression of the CNS
– this is the basic cause of adverse effects
Low doses - drowsiness, impaired judgment,
diminished motor skils.
Overdoses (deliberate)- toxicities .
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Medical Toxicants
16. Sedative and hypnotics cont’d,...
Barbiturates belong to a class of sedative-
hypnotic drugs with
abuse potential &
a recognized withdrawal syndrome.
Toxic manifestations of barbiturates vary with
the
amount of ingestion,
type of drug and
time elapsed since ingestion. 4/5/2022
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Medical Toxicants
17. Sedative and hypnotics cont’d,...
Barbiturate poisonings are
common in intentional ( suicidal) poisoning but
less frequently encountered in accidental poisoning.
Over 70% suicides that occur annually are
related to
barbiturate overdose (alone or with alcohol).
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Medical Toxicants
18. Sedative and hypnotics cont’d,...
Lower doses of short acting barbiturates (E.g.
pentobarbital) than the long-acting barbiturates
(e.g. Phenobarbital) generally cause toxicity.
Mild intoxication resembles that of alcohol
intoxication.
Moderate intoxication is characterized by
greater depression of mental status and
severe intoxication causes coma.
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Medical Toxicants
19. Sedative and hypnotics cont’d,...
Management of barbiturate poisoning
Stabilization
Patent airway
Adequate ventilation
Keeping the patient warm
Cardiovascular support
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20. Sedative and hypnotics cont’d,...
Enhancing drug elimination & ↓g
absorption
Gastric lavage- If no more than 2-4 hours
have passed since ingestion of the
barbiturate,
gastric lavage is done.
Activated charcoal- 1g/Kg-1 is administered
through nasogastric tube;
Cathartic can be used along with it for further
removal of barbiturates.
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21. Sedative and hypnotics cont’d,...
Multidose activated charcoal (MDAC)
increases the clearance and
decreases the half-life of phenobarbital.
Forced alkaline diuresis:
especially useful in long acting barbiturates
which are largely excreted by the kidney
(phenobarbital) (NaHCO3 1-2 meq/kg every 4-
6 hr).
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22. Sedative and hypnotics cont’d,...
Hemodialysis-
Single six hour haemodialysis can remove an
amount of barbiturate
which is comparable to that removed during
24 hours of sustained diuresis.
Hemodialysis is recommended if
renal or cardiac failure,
electrolyte abnormalities, or
acid-base disturbances occur,
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23. Sedative and hypnotics cont’d,...
↑s the frequency of the opening of the chloride
channels &
facilitate the actions of GABA.
At high doses, induce NM blockade and
cause vasodilation & hypotension (after i.v. administration).
Do not significantly alter ventilation, except in:
Patients with respiratory complications
Elderly population
Presence of alcohol or other S/H.
Minimal effect on cardiovascular integrity.
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Medical Toxicants
24. Sedative and hypnotics cont’d,...
Mild toxicity:
ataxia, drowsiness, and motor incoordination,
paranoia or erratic behavior and is easily
aroused.
Moderate toxicity:
patient is aroused by verbal stimulation,
although he or she may enter coma stage one
or two.
Severe toxicity:
unresponsive except to deep pain stimulation
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Medical Toxicants
25. Sedative and hypnotics cont’d,...
Clinical management
is symptomatic and
may also incorporate the use of a specific
antidote.
Flumazenil,
is a benzodiazepine antagonist.
completely reverses the sedative, anxiolytic,
anticonvulsant, ataxic, anesthetic, comatose, and
muscle relaxant effects.
dministration of 0.2 to 1.0 mg i.v.
has an acute onset of 1 to 3 min and
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Medical Toxicants
27. Drugs of abuse
The term `drug abuse` connotes social
disapproval.
Any use of a drug for non-medical purposes,
usually for altering consciousness
but also for body building is known as abuse of
drug.
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Medical Toxicants
28. Drugs of abuse cont’d,...
The main features of drugs of abuse:
Psychological dependence (drug seeking
behavior in which the individual uses the drug
repetitively for personal satisfaction),
physiologic dependence (withdrawal of the drug
produces symptoms & signs), &
tolerance (necessitating large doses of the drug
to achieve the same response).
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Medical Toxicants
29. Opioids comprise a broad spectrum of
substances that include
opiate alkaloids (e .g morphine &codeine),
synthetic opioids (e .g pethidine) &
semi synthetic opioids (e .g heroin).
They exert their effect acting on
opiate receptors located within the CNS
resulting in analgesia & euphoria.
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Medical Toxicants
30. Opioid /morphine toxicities cont’d,...
Opioids are used to treat
cough, diarrhea, dyspnea (congestive heart failure),
and
sometimes anxiety as well as pain.
The most commonly abused drugs in this group
are
heroin and
morphine.
Tolerance and dependence of opioids develop with
chronic use.
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Medical Toxicants
31. Opioid /morphine toxicities cont’d,...
Common scenarios of poisoning
Accidental ingestion (children)
Therapeutic misadventures (acute or chronic
accidental overmedication)
Unintentional overdosing by drug abusers
Suicidal use
Illicit drug users, sellers, or smugglers
(intoxicated after ingesting drug packages or
packaging them in body cavities).
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Medical Toxicants
32. Opioid /morphine toxicities cont’d,...
The classic triad for opioid poisoning is
miosis,
coma and
respiratory depression.
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Medical Toxicants
33. Opioid /morphine toxicities cont’d,...
Management of opoid poisoning
Maintenance of vital functions,
including respiratory and cardiovascular
integrity
An IV line & continuous cardiac and
respiratory monitoring
Supplementary oxygen and
assisted ventilation
Gastric lavage and induction of emesis
are effective if treatment is instituted soon after
ingestion 4/5/2022
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Medical Toxicants
34. Opioid /morphine toxicities cont’d,...
Naloxone
IV in a dose of 0.03 mg/kg/dose
provides both therapeutic & diagnostic modality
for opioid poisoning (reverses respiratory and CNS
depression).
Naltrexone
is also a pure opioid antagonist available as oral
tablet dosage form only.
A 50-mg dose of naltrexone blocks the
pharmacological effects of opioids by competitive
binding at opioid receptors.
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Medical Toxicants
35. Opioid /morphine toxicities cont’d,...
Fluid resuscitation and pressor therapy
may be necessary for hypotension.
Ventricular tachycardia should be treated
with
lidocaine, propranolol
Coma & seizure
diazepam, phenytoin, or a barbiturate may help.
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Medical Toxicants
36. Nicotine
is one of the most widely abused chemical
and now
considered to be one of the most addicting
substances. It is the principal
pharmacologically active component of
tobacco.
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Medical Toxicants
37. Nicotine toxicity cont’d,...
Nicotine poisoning may occur
in accidental ingestions of tobacco products
(especially by children),
use of nicotine-containing gums, and
industrial exposure to tobacco products,
contact with some pesticides and so on.
Nicotine has both stimulant and depressant
action.
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Medical Toxicants
38. Nicotine toxicity cont’d,...
Nicotine is readily absorbed
through intact skin as well as
through mucus membranes and the respiratory
tract.
It is metabolized by the liver and excreted by the
kidney.
Victims can complain
at low doses nausea, emesis, excessive
salivation, and diarrhea .
But at high dose it can cause respiratory
paralysis, cardiovascular collapse and
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Medical Toxicants
40. Exert their actions primarily
by antagonizing dopamine receptors.
Affect central pathways associated with
skeletal movt., hallucinations & delusions, psychosis&
prolactine release.
Affinities for non dopaminergic sites, such as
cholinergic, α1-adrenergic & histaminic receptors.
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Medical Toxicants
41. Antipsychotics cont’d,...
Display
sedation,
muscle relaxation &
lowering of seizure threshold.
Depress the reticular activating system (RAS)
responsible for stimulating wakefulness (consciousness)
& eliciting arousal reflexes.
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Medical Toxicants
42. Antipsychotics cont’d,...
Have antimuscarinic & antihistaminic effects
such as
mydriasis, dry mouth, tachycardia & ↓d GI activity.
Vasodilation, orthostatic hypotension
α-adrenergic blockade contributes to
hypotension.
Quinidine-like CV AV block
precipitates potentially fatal ventricular arrhythmias
& cardiac arrest.
EP signs and symptoms develop when an
imbalance b/n
antidopaminergic (greater) & anticholinergic activity
is created. 4/5/2022
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Medical Toxicants
44. Antipsychotics cont’d,...
Acute dystonic reactions (95% of patients,
predominantly young males)
Akathisia affects mostly elderly patients
Parkinsonism develops and affects 90% of
patients.
Risk of developing a tardive disorder ↑s as
duration & dose ↑se.
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Medical Toxicants
45. Antipsychotics cont’d,...
CLINICAL MANAGEMENT OF ACUTE OVERDOSE
EPS
are not fatal &
are best treated with anticholinergics or BZDs.
Several days of treatment
to reverse acute dystonic reactions.
Tardive dyskinesia is difficult to manage,
if symptoms appear at doses
Drug discontinuation and
Substitution with an atypical neuroleptic, such as
clozapine.
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Medical Toxicants
46. Antipsychotics cont’d,...
Treatment for reversing neuroleptic induced
hypotension and quinidine-like effects, especially
ventricular dysrhythmias,
is similarly managed with lidocaine & NaHCO3.
Convulsions or hyperactivity
is controlled with pentobarbital or diazepam.
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