Poisoning by specific pharmaceutical agents

1
Poisoning by specific pharmaceutical agents

• Dr. Mohamed shekhani

2
Paracetamol

• Acetaminophen) is the drug most commonly used
  in overdose.
• Toxicity results from formation of an
  intermediate reactive metabolite which binds
  covalently to cellular proteins, causing cell
  death , results in hepatic occasionally
  renal failure.
• In therapeutic doses, the toxic intermediate
  metabolite is detoxified in reactions
  requiring glutathione, but in overdose,
  glutathione reserves become exhausted.

3
Management

• Activated charcoal used in patients
  presenting within 1 hour.
• Antidotes act by replenishing hepatic
  glutathione.
• Acetylcysteine IV (or orally in some
  countries) is highly efficacious if
  administered within 8 hours of the overdose.
• The efficacy declines thereafter, administration
  should not be delayed in patients presenting
  after 8 hours to await a paracetamol blood
  concentration result.
• The antidote can be stopped if the paracetamol
  concentration is shown to be below the
  appropriate treatment line.
• The most important adverse effect is related to
  dose-related histamine release, the
  anaphy-actoid reaction, with itching /
  urticaria,in severe cases, bronchospasm/
  hypotension,managed by temporary
  discontinuation an antihistamine.
• An alternative antidote is methionine 2.5 g
  orally 4-hourly to a total of four doses, less
  effective, especially if delayed.

4
Management

• If a patient presents gt15 hours after ingestion,
  liver function tests, PT(or INR), renal
  function tests a venous bicarbonate should be
  measured, the antidote started a poisons
  information centre or local liver unit
  contacted for advice if results are abnormal.
• ABG should be taken in patients with severe liver
  function abnormalities as metabolic acidosis
  indicates severe poisoning.
• Liver transplantation should be considered in
  individuals who develop life- threatening liver
  failure.
• If multiple ingestions of paracetamol have taken
  place over several hours or days (i.e. a
  staggered overdose), acetylcysteine should be
  given when the paracetamol dose exceeds 150
  mg/kg /any one 24-hour period or 75 mg/kg in
  high-risk groups

5
(No Transcript)
6
(No Transcript)
7
Salicylates (aspirin)

• Commonly causes nausea, vomiting, sweating,
  tinnitus , deafness.
• Direct stimulation of the respiratory centre
  produces hyperventilation respiratory alkalosis.
  
• Peripheral vasodilatation with bounding pulses
  profuse sweating occurs in moderately severe
  poisoning.
• Serious salicylate poisoning is associated with
  metabolic acidosis, hypoprothrombinaemia,
  hyperglycaemia, hyperpyrexia, renal failure,
  pulmonary oedema, shock cerebral oedema.
• Agitation, confusion, comafits may occur,
  especially in children.
• Toxicity is enhanced by acidosis, which increases
  salicylate transfer across the BBB.

8
Management

• Activated charcoal should be administered if
  presents early.
• Multiple doses of activated charcoal may enhance
  salicylate elimination but currently are not
  routinely recommended.
• The plasma salicylate concentration should
  be measured at least 2 (in symptomatic
  patients) or 4 hours (asymptomatic patients)
  after overdoserepeated in patients with
  suspected serious poisoning, since it may
  continue to rise some hours after .
• In adults, concentrations gt500 -700 mg/L suggest
  serious life-threatening poisoning
  respectively, but clinical status is more
  important assessing severity.
• Dehydration should be corrected carefully, as
  there is a risk of pulmonary oedema.
• Metabolic acidosis should be identified and
  treated with iv sodium bicarbonate (8.4), once
  plasma potassium has been corrected.
• Urinary alkalinisation is indicated for adults if
  salicylate gt500 mg/L.

9
Management

• Haemodialysis is very effective at removing
  salicylate correcting acidbase fluid
  balance abnormalities should be considered when
  
• Serum concentrations gt700 mg/L in adult
  patients with severe toxic features
• Or when there is renal failure
• Pulmonary oedema,
• Coma
• Convulsions
• Refractory acidosis

10
Tricyclic antidepressants (TCAs)

• TCAs used frequently in overdose
• It carries a high morbidity/mortality relating to
  their sodium channel-blocking, anticholinergic
  a-adrenoceptor-blocking effects

11
Clinical features

• Anticholinergic effects are common .
• Life-threatening complications are frequent,
  including convulsions, coma, arrhythmias
  (ventricular tachycardia, ventricular
  fibrillation , less commonly, heart block)
  hypotension, which results from inappropriate
  vasodilatation or impaired myocardial
  contractility.
• Serious complications appear to occur more
  commonly with dosulepin amitriptyline.

12
Management

• Activated charcoal should be given if presents
  sufficiently early.
• All patients with possible TCAD overdose should
  have a 12-lead ECG ongoing cardiac monitoring
  for at least 6 hours.
• Prolongation of the QRS interval (especially if gt
  0.16 s) indicates severe sodium channel
  blockade associated with an increased risk
  of arrhythmia .
• ABGs be measured in patients with suspected
  severe poisoning.
• In patients with arrhythmias, severe ECG effects
  or acidosis, IV sodium bicarbonate (50 mL of
  8.4 solution) should be administered repeated
  to correct pH.
• The correction of the acidosis sodium loading
  that result is often associated with rapid
  improvement in ECG arrhythmias.
• Hypoxia electrolyte abnormalities should also
  be corrected.
• Anti-arrhythmic drugs should only be given on
  specialist advice.
• Prolonged convulsions should be treated with IV
  benzodiazepines.

13
Cardiotoxic drugs
14
Antipsychotics

• Often prescribed for patients at high risk of
  self-harm or suicide, commonly encountered in
  overdose.

15
Clinical features

• Drowsiness, tachycardia,hypotension are
  frequently found.
• Anticholinergic features acute dystonias (e.g.
  oculogyric crisis, torticollis trismus) may
  occur after overdose with typical
  antipsychot-ics such as haloperidol or
  chlorpromazine.
• QT interval prolongation torsades de pointes
  may occur with some antipsychotics, either
  typical (e.g. thioridazine, haloperidol) or
  atypical (e.g. quetiapine, ziprasidone).
• Convulsions may occur.

16
Management

• Activated charcoal may be of benefit if given
  sufficiently early.
• Cardiac monitoring should be undertaken for
  at least 6 hours.
• Management is largely supportive, with
  treatment directed at complications

17
Antidiabetic agents

• Commonly causing toxicity in over-dose include
  the sulphonylureas (chlorpropamide,
  glibenclamide, gliclazide, glipizide,
  tolbutamide), biguanides (metformin and
  phenformin) insulins.

18
Clinical features

• Sulphonylureas parenteral insulin cause
  hypoglycaemia when taken in overdose, but insulin
  is non-toxic if ingested.
• The duration of hypoglycaemia depends on the
  half-life or release characteristics of the
  preparation may be prolonged over several
  days with long-acting agents such as
  chlorpropamide, insulin zinc suspension or
  insulin glargine.
• Features of hypoglycaemia include nausea,
  agitation, sweating, aggression, behavioural
  disturbances, confusion, tachycardia,
  hypothermia, drowsiness, coma or convulsions .
• Permanent neurological damage can occur if
  hypoglycaemia is prolonged.
• Hypoglycaemia can be diagnosed using bedside
  glucose strips but venous blood should also be
  sent for laboratory confirmation.

19
Clinical features

• Metformin is uncommonly associated with
  hypoglycaemia.
• Its major toxic effect in overdose is lactic
  acidosis, which can be associated with a
  high mortality, particularly common in elder
  those with renal or hepatic impairment, or
  ethanol coingestion.
• Other featuresare nausea ,vomiting, diarrhoea,
  abdominal pain, drowsiness, coma, hypotension
  CV collapse.

20
Management

• Activated charcoal should be considered for all
  patients who present within 1 hour of ingestion
  of a substantial overdose of an oral
  hypoglycaemic agent.
• Venous blood glucose, urea, electrolytes
  should be measured repeated regularly.
• Hypoglycaemia should be corrected using oral
  or IV glucose (50 mL of 50 dextrose) an
  infusion of 1020 dextrose may be required
  to prevent recurrence.
• Intramuscular glucagon can be used as an
  alternative, especially if IV access is
  unavailable.
• Failure to regain consciousness within a few
  minutes of normalisation of the blood glucose can
  indicate (CNS) depressant has also been
  ingested, the hypoglycaemia has been
  prolonged, or there is another cause for the
  coma (e.g. cerebral haem-orrhage or oedema).

21
Management

• ABG should be taken after metformin overdose
  to assess the extent of acidosis.
• If present, plasma lactate should be measured
  acidosis should be corrected with intravenous
  sodium bicarbonate (e.g. 250 mL 1.26 solution or
  50 mL 8.4 solution, repeated as necessary).
• In severe cases haemodialysis or
  haemo-diafiltration is used.

22
Organophosphorus (op) insecticides/ nerve
agents

• Widely used as pesticides, especially in
  developing countries.
• The case fatality rate following deliberate
  ingestion of OP pesticides in devel-oping
  countries in Asia is 520.
• Nerve agents developed for chemical warfare
  are derived from OP insecticides but are much
  more toxic.
• G agents are volatile, are absorbed by
  inhalation or via the skindissipate rapidly
  after use.
• V agents are contact poisons unless
  aerosolised,contaminate ground for weeks or
  months.
• The toxicology and management of nerve
  agentpesticide poisoning are similar.

23
Mechanism of toxicity

• OP compounds phosphonylate the active site
  of acetylcholinesterase (AChE), inactivating the
  enzyme,leading to the accumulation of
  acetylcholine (ACh) in cholinergic synapses.
• Spontaneous hydrolysis of the OP-enzyme complex
  allows reactivation of the enzyme.
• Loss of a chemical group from the OP-enzyme
  complex prevents further enzyme
  reactivationageing),after which,
  praladoxime(enzyme reactivator will not be
  effective) new enzyme needs to be synthesised
  before function can be restored. The rate of
  ageing is is more rapid with dimethyl compounds
  (3.7 hours) than diethyl compounds (31
  hours),especially rapid after exposure to
  nerve agents (soman in particular), which
  cause ageing within minutes.

24
Clinical features

• OP poisoning causes an acute cholinergic phase,
  occasionally followed by the intermediate
  syndrome or organophosphate-induced delayed
  polyneuropathy (OPIDN).
• The onset, severity and duration of
  poisoning depend on the route of exposure agent
  involved.

25
Clinical features

• Acute cholinergic syndrome
• Usually starts within a few minutes of
  exposure.
• Nicotinic or muscarinic features may be
  present.
• Vomiting ,profuse diarrhoea are typical
  following oral ingestion.
• Bronchoconstriction, bronchorrhoea and
  salivation may cause severe respiratory
  compromise.
• Miosis is characteristic muscle fasciculations
  strongly suggests the diagnosis, although often
  absent, even in serious poisoning.
• Subsequently, generalised flaccid paralysis
  which can affect respiratory ocular
  muscles result in respiratory failure.
• Ataxia, coma,convulsions may occur.
• In severe poisoning, cardiac repolarisation
  abnormalities torsades de pointes may occur.
• Other early complications include
  extrapyramidal features, pancreatitis, hepatic
  dysfunction pyrexia.

26
Management

• If external contamination, further exposure
  should be prevented, contaminated
  clothingcontact lenses removed, the skin washed
  with soap and water the eyes irrigated.
• The airway should be cleared of excessive
  secretions high-flow oxygen administered.
• Intravenous access should be obtained.
• Gastric lavage or activated charcoal may be
  considered within 1 hour of ingestion.
• Convulsions should be treated
• The ECG, oxygen saturation, blood gases,
  temperature, urea , electrolytes, amylase,
  glucose should be monitored closely.
• Early use of sufficient doses of atropine is
  potentially lifesaving in patients with
  severe toxicity.
• Atropine reverses ACh-induced bronchospasm

27
Management

• Atropine reverses ACh-induced
  bronchospasm,bronchorhea, bradycardia
  ,hypotension.
• A marked increase in heart rate associated
  with skin flushing after a 1 mg intravenous dose
  makes OP poisoning unlikely.
• In OP poisoning, atropine should be administered
  in doses of 0.62 mg i.v., repeated every 1025
  mins until secretions are controlled, the
  skin is dry and there is a sinus tachycardia.
• Large doses may be needed but excessive doses
  may cause anticholinergic effects.
• In patients requiring atropine, an oxime
  such as pralidoxime chloride (or obidoxime), if
  available, should also be administered, as this
  may reverse or prevent muscle weakness,
  convulsions or coma, especially if administered
  rapidly after exposure.
• The dose for an adult is 2 g i.v. over 4 mins,
  repeated 46-hourly.

28
Management

• Oximes re-activating AChE that has not undergone
  ageing are less effective with dimethyl
  compounds nerve agents, especially soman.
• Oximes may provoke hypotension, especially if
  rapidly.
• Ventilatory support should be instituted
  before the patient develops respiratory
  failure .
• Benzodiazepines may be used to reduce
  agitation,fasciculations, treat
  convulsionssedate patients during mechanical
  ventilation.
• Exposure is confirmed by measurement of
  plasma (butyrylcholinesterase) or red blood cell
  cholinesterase activity. ,correlate poorly with
  the severity of clinical features, although
  values are usually less than 10 in severe
  poisoning, 2050 in moderate poisoning ,gt 50 in
  subclinical poisoning.
• The acute cholinergic phase usually lasts 4872
  hours, with most patients requiring intensive
  cardiorespiratory support monitoring.

29
Ethylene glycol/Methanol

• Found in antifreeze, brake fluids and, in
  lower concentrations, windscreen washes.
• Methanol is present in some antifreeze
  products commercially available industrial
  solvents, methylated spirits,illi-citly produced
  alcohol.
• Both are rapidly absorbed after ingestion.
• They are converted via alcohol dehydrogenase to
  toxic metabolites largely responsible for their
  clinical effects.
• are no longer detectable.

30
Clinical features

• Early feature ataxia, drowsiness, dysarthria and
  nystagmus, often associated with vomiting.
• As the toxic metabolites are formed, metabolic
  acidosis, tachypnoea, coma,seizures may develop.
• Toxic effects of ethylene glycol toxicity include
  
• ophthalmoplegia, cranial nerve palsies,
  hyporeflexia ,myoclonus.
• Renal pain / acute tubular necrosis occur because
  of renal precipitation of calcium oxalate .
• Hypocalcaemia, hypomagnesaemia,hyperkalaemia are
  common.
• Methanol poisoning features
• headache, confusion , vertigo.
• Visual impairment photophobia develop.
• Blindness may be permanent, although some
  recovery may occur
• Pancreatitis abnormal liver function reported.

31
Management

• Urea, electrolytes, chloride, bicarbonate,
  glucose, calcium, magnesium, albuminplasma
  osmolarity,ABG, should be measured in all
  patients.
• The osmolal anion gaps should be calculated.
• Initially, poisoning is associated with an
  increased osmolar gap, but as toxic metabolites
  are produced, an increased anion gap associated
  with metabolic acidosis will develop.
• The diagnosis can be confirmed by measurement of
  ethylene glycol or methanol concentrations,but
  not widely available.
• An antidote, either ethanol or fomepizole,
  should be administered to all patients with
  suspected significant exposure while awaiting
  the results of laboratory investigations.
• These block alcohol dehydrogenasedelay the
  formation of toxic metabolites until the drug
  is eliminated naturally or by dialysis.

32
Management

• The antidote should be continued until ethylene
  glycol or methanol concentrations are
  undetectable.
• Metabolic acidosis should be corrected with
  sodium bicarbonate
• (e.g. 250 mL of 1.26 solution, repeated as
  necessary).
• Convulsions should be treated with an IV
  benzodiazepine.
• In ethylene glycol poisoning, hypocalcaemia
  should only be corrected if there are
  severe ECG features or seizures occur, since this
  may increase calcium oxalate crystal formation.
• Haemodialysis or haemodiafiltration should be
  used in severe poisoning, especially if
  renal failure is present or there is visual
  loss in the context of methanol poisoning.
• It should be continued until acute toxic features
  are no longer present and ethylene glycol or
  methanol concentrations are not detectable.

33
CO poisoning

• CO is a colourless / odourless gas produced by
  faulty appliances burning organic fuelsvehicle
  exhaust fumes,house fires smoke.
• It causes toxicity by binding with
  haemoglobin cytochrome oxidase, which reduces
  tissue oxygen deliveryinhibits cellular
  respiration.
• It is a common cause of death by poisoning most
  patients who die before reaching hospital.

34
CO poisoning Clinical features

• Early clinical features headache, nausea,
  irritability, weakness tachypnoea, are non-
  specific, so correct diagnosis will not be
  obvious if the exposure is occult, e.g. faulty
  domestic appliance.
• Subsequently, ataxia, nystagmus, drowsiness and
  hyperreflexia may develop, progressing to coma,
  convulsions, hypotension, respiratory
  depression, cardiovascular collapse death.
• Myocardial ischaemia may result in arrhythmias or
  AMI.
• Cerebral oedema is common rhabdomyolysis may
  lead to myoglobinuria renal failure.
• In those who recover from acute toxicity,
  longer-term neuropsychiatric effects are
  common,as personality change, memory loss ,
  concentration impairment,extrapyramidal effects,
  urinary or faecal incontinence, gait disturbance.
  
• Poisoning during pregnancy may cause fetal
  hypoxia intrauterine death.

35
CO poisoning Management

• Patients should be removed from exposure as
  soon as possible resuscitated as necessary.
  
• Oxygen should be administered in as high a
  concentration as possible via a tightly
  fitting facemask, as this reduces the
  half-life of carboxyhaemoglobin from 46
  hours to about 40 minutes.
• Measurement of carb-oxyhaemoglobin is useful
  for confirming exposure, but results do not
  correlate well with the severity of poisoning,
  partly because concentrations fall rapidly after
  removal of the patient from exposure, especially
  if supplemental oxygen has been given.
• An ECG should be performed in all patients
  with acute poisoning, especially those with
  pre-existing heart disease.
• Arterial blood gas analysis should be checked in
  those with serious poisoning.

36
CO poisoning Management

• Oxygen saturation readings by pulse oximetry
  are misleading since both carboxyhaemoglobin
  oxyhaemoglobin are measured.
• Excessive IVF should be avoided, particularly
  in the elderly, because of the risk of pulmonary
  cerebral oedema.
• Convulsions should be controlled with diazepam.
• Hyperbaric oxygen therapy is controversial.
• In theory, at 2.5 atmospheres, it reduces the
  half-life of carboxyhae-moglobin to 20 minutes
  increases the amount of dissolved oxygen by a
  factor of 10.

37
Single-best choice MCQs

• 1.The antidote of paracetamol can be only be
  given
• A.Oraly alone.
• B. IV alone.
• C.Rectally.
• D.IM.
• E. IV / or orally.

38
Single-best choice MCQs

• 2. The antidote of paracetamol
• A.Replenishes glutathione liver stores.
• B. Activates drug metabolizing enzymes.
• C. Inhibits drug metabolizing enzyme.
• D.All.
• E.None.

39
Single-best choice MCQs

• 3. The paracetamol antidote should be given
  within
• A. 16 hours.
• B. 4 hours.
• C. 8 hours.
• D. 24 hours.
• E.35 hours.

40
Single-best choice MCQs

• 4.Paracetamol drug level in paracetamol poisoning
  is best measured after ingestion of
• A. 16 hours.
• B. 4 hours.
• C. 8 hours.
• D. 24 hours.
• E.35 hours.

41
Single-best choice MCQs

• 5.Paracetamol poisoning causes
• A.Heopatic failure alone.
• B. Renal failure.
• C. Both.
• D. Neither.
• E. Respiratory failure.

42
Single-best choice MCQs

• 6.High risk for paracetamol poisoning with lower
  doses include all the following except
• A. Chronic alcoholics.
• B. Eating disorders patients.
• C. Epileptics on treatment.
• D. Asthmatics.
• E. Maluarished persons.

43
Single-best choice MCQs

• 7. In symptomatic aspirin poisoning patients drug
  level is best taken after ingestion of
• A. 2 HOURS.
• B.4 hours.
• C.6 hours.
• D.8 hours.
• E.10 hours.

44
Single-best choice MCQs

• 8. In symptomatic aspirin poisoning patients,
  hemodialysis is indicated if blood level is
  above
• A. 400 mgm/l.
• B. 300 mgm/l.
• C 200 mgm/l.
• D. 600 mgm/l.
• E. 700 mgm/l.

45
Single-best choice MCQs

• 9. The most serious effects of aspirin poisoning
  is
• A. Hypoglycemia.
• B.Hypocalcemia.
• C. Metabolic acidosis.
• D. Respiratory alkalosis.
• E.Bleeding tendencies.

46
Single-best choice MCQs

• 10.All these drugs are cardiotoxic if taken in
  overdose except
• A.Trcyclic antidepressants.
• B.Antipsychotics.
• C. CO.
• D.Paracetamol.
• E.SSRI.

47
Single-best choice MCQs

• 11.Oximes are least effects in organophosphorous
  poisoning with
• A. Soman.
• B.Dimethyl compounds.
• C. Diethyl compounds.
• D. All.
• E.None.

48
Single-best choice MCQs

• 12.CO poisoning is best diagnosed by
• A.Pulseoximetry.
• B. Carboxyhemoglobin blood level.
• C. Clinical features.
• D.All.
• E.Neither.

49
Single-best choice MCQs

• 13. CO poisoning is best treated by
• A. Usual ward oxygen.
• B. Hyperbaric oxygen.
• C. Only supportive measures.
• D. All.
• E. None.
•