Toxicology

1. 1
4/5/2022
Medical Toxicants

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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Medical Toxicants

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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Medical Toxicants

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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Medical Toxicants

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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Medical Toxicants

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

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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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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

43. Antipsychotics cont’d,...
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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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