1. Drug overdose
and It’s Management
Dr T Mohanavel
Asst Professor
Department of general medicine
Namakkal Medical College
2. Humans takea numberof drugs for health reasons, it is practically
guaranteed that all useful drugs will produce unwanted effects, but some
can produce positively dangerous effects.
Toxicity refers to these sometimes deadly effects: though all drugs
have adverse effects at normal doses, it is only the dangerous ones which
are referred to as toxic.
These are the result of excessive pharmacological action of the
drug due to overdosing or prolonged use.
2
3. Toxicity may result from extension of the therapeutic effect of the drug, e.g.
Coma by barbiturates, complete A-V block by digitoxin, bleeding due to
heparin, etc.
The CNS, CVS, kidney, liver, lung, skin and blood forming organs are most
commonly involved in drug toxicity.
3
4. Drug will do more harm than good in an individual patient depending on
many factors, including the patient’s age, genetic makeup and preexisting
conditions, the dose of the drug administered, and other drugs the
patient may be taking.
On-target adverse effects, which are the result of the drug binding to its
intended receptor, but at an inappropriate concentration, with suboptimal
kinetics, or in the incorrect tissue
Off-target adverse effects, which are caused by the drug binding to a target or
receptor for which it was not intended
Production of toxic metabolites.
4
6. Lethal dose (LD50)
LD50
(lethal dose, 50%). This is
defined as the dose required
to kill half the members of
a specific animal
population when entering the
animal’s body by a particular
route. LD50 is a
general indicator of a substance’s toxicity
within a short space of time. It is a measure of
acute toxicity.
6
7. The first line of defence is to remove the drug from the patient before it is fully
absorbed, and techniques include:
Irrigation to remove drugs applied to the eyes or skin.
Gastric lavage, where the stomach is washed out and
drained using tubes.
Activated charcoal, which is swallowed and soaks up the drug
from the gut.
Ipecac syrup, which causes vomiting in order to empty the
stomach.
Cathartics, laxatives which purge the drug from the gut.
7
8. A second line of defence involves the removal of the drug
from the bloodstream by various methods, including:
Changing urine pH to increase excretion of the drug into the urine.
Forced diuresis, where drugs are given to increase urine production.
Haemodialysis, where the blood is passed through a machine to remove
the drug.
Exchange transfusion to replace the patient's drug-filled
blood with fresh blood.
8
11. Paracetamol poisoning
Most common tablet involved in toxicologic fatalities
Available worldwide has over the counter analgesic &
antipyretic
Toxic dose 140 mg/KG for adult
Pathophysiology
95% metabolised via Glucoronidation and sulphation as non
toxic conjugate product
5% via cytochrome p 450 pathway into toxic intermediate
NAPQI
Depletion of Glutathione reserve ->ROS->CENTRI LOBAR HEPATIC
NECROSIS
15. Treatment
Gastric lavage
activated charcoal 1 gram per kg within 4 hours of ingestion
specific Antidote : N ACETYL CYSTEINE
Administered within 8 hours of ingestion
Oral loading dose 140 mg /kg then 70 mg/kg every four hours
for total of 17 doses
IV loading dose 150 mg /kg+ 200 ml D5W over 15 minutes
maintenance dose 50 mg/kg + 500 ml D5W over next 4 hours
100 mg/kg + 1000 ml D5W over next 16 hours
16. Special Precautions
In chronic alcoholic it is recommended that NAC treatment is
administered at 50% below the upper toxic line of
nomograms
Close monitoring for
hypoglycemia
electrolyte disturbance
GI bleed
cerebral edema
18. Phenytoin poisoning
First line treatment for seizure
most commonly used drug - sodium channel blocker
Extensively bound to serum proteins mainly albumin only the
unbound free fraction exerts pharmacological action
neonate ,urimic patient, hypo albuminenia are more prone to
intoxication
Toxic dose 20Mg/kg
19. Clinical manifestations
Acute toxicity is associated with neurological syndrome of
cerebellar origin cardio toxicity reported with Rapid IV
administration Like Hypotension cardiac arrest
plasma concentration
>15microgram/ml Nystagmus Dipolopia
>30 Ataxia Dysarthria
>50 movement disorder confusion coma
Extravasation Purple Glove syndrome
22. Why so important
Intentional salicylate overdose usually occurs predominantly in
adolescents & young adults.
Overdoses in children are usually accidental & in the elderly they
occur as therapeutic misadventures.
The severity of aspirin overdose is often underestimated by ER
personnel because of lack of familiarity.
This is an important problem because delay in treatment of
severe intoxication is associated increased mortality in severe
cases.
With good management mortality rates are low but even at best about
5% of severely toxic patients die, usually from cardiovascular & central
nervous system complications.
23. Therapeutic Uses Of Salicylates
▶ Analgesics
▶ Anti inflammatorys
▶ Antipyretics
▶ Keratolytics
▶ Antiplatelets.
24. Salicylate Product Strengths
▶ Adult Aspirin (300mg, 325 mg)
▶ Baby Aspirin (81 mg)
▶ Bismuth subsalicylate syrup
1 ml is equivalent to 8.77 mg of salicylic acid.
60 ml is equivalent to a therapeutic dose (650 mg) of aspirin.
▶ Methylsalicylate Topical
1 teaspoonful (100% MS) = 21 adult strength aspirin
25. Inherent Toxicity
▶ Aspirin
Toxic dose = 150 mg/kg
Minimal lethal dose = 450 mg/kg
▶ Methylsalicylate
Lethal dose in children = 4 cc of 100% MS
Lethal dose in adults = 6 cc of 100% MS
26. Chronic vs Acute Salicylate
Poisoning
Acute Chronic
▶ Victim Y
oung Adult Elderly
▶ Circumstances Intentional Accidental
▶ Time T
o Diagnosis Short Long
▶ Mortality 2% 25%
▶ Morbidity 16% 30%
29. PHARMACOKINETICS
▶ Absorbed rapidly by passive diffusion.
▶ 90 % Binds to albumin .
▶ Has a very short half-life (30 min).
▶ Metabolized by the liver. (hepatic conjugation with glycin or glucuronic acid).
▶ Excreted in the urine (PH dependent).
30. Metabolic Disturbance
▶ Hyperthermia.
▶ Acid-base disturbances (respiratory alkalosis, metabolic acidosis)
▶ Dehydration
▶ Electrolyte imbalance (hypokalemia, hyponatremia)
▶ Altered glucose levels (elevated, normal, or low; CNS glucose concetrations
may be low despite normal or even high blood glucose concentrations)
38. Treatment
▶ Fluid resuscitation :
-Correction of dehydration with 0.9% sodium chloride or lactated Ringer solution,
10 to 20 mL/kg/h over 1 to 2 hours until a good urine flow is established of at least
2 to 3 mL/kg/h
▶ GI decontamination:
- Gastric lavage in the first hr (warmed NS 38C,protect airway)
- Activated charcoal in the first 4 hr, 1-2g/kg (maximum 100g)
- Whole-bowel irrigation (WBI) with polyethylene glycol(enteric coated or
slow release formulas, 2 L/h (20 mL/kg/h until the rectal effluent is clear)
▶ Urinary alkalinization with sodium bicarbonate:
- Moderate to sever toxicity.
- 1 to 2 mEq/kg of sodium bicarbonate IV bolus, then infusion of DW5% with 100 to
150 mEq of sodium bicarbonate and 20 to 40 mEq of potassium chloride in each liter
at a rate of 1.5 to 2.5 mL/kg/h.
- Goal urine output is 2 to 3 mL/kg/h.
39. ▶ Hemodialysis:
- Management of patients with salicylate poisoning and a serum salicylate level
>100 mg/dL after acute ingestion or >40 mg/dL after chronic ingestion, altered mental
status, renal failure, pulmonary edema, progressive clinical deterioration, refractory
acidosis, or failure to respond to more conservative therapy.
40. Prognosis
▶ The prognosis in patients with acute salicylate poisoning is very good: the
mortality rate is 1%, and the morbidity rate is 16%
▶ The prognosis is worse in patients with chronic salicylate poisoning: the
mortality rate is 25%, and the morbidity rate is 30%
42. 🞇 The mother was tending to her newborn infant when the child
grabbed his mom's bottle of iron pills (ferrous sulfate 325
mg) from the counter. The iron pill contains 65 elemental
iron per pill. He ate them thinking they looked like candy.
There were 15 tablets missing this means 975 elemental iron
ingested.
🞇 Physician performed abdominal plain x ray that revealed
radiopaque tablets in the stomach and intestine.
43.
44. Diagnostic Work up:
Patients Requiring Assessment
🞇 Ingestion of > 40 mg/kg elemental iron. (approximately
> ½ tablet/kg or 6.5 ml syrup/kg).
🞇Ingestion of an unknown quantity.
🞇Any symptomatic patients
The following investigations should be done:
45. Diagnostic investigation:
🞇 Abdominal XR (if tablets ingested).
🞇 Serum iron.
Serum iron level:
🞇 Serum iron levels generally correlate with clinical severity and are
as follows:
Mild - Less than 300 µg/dl
Moderate - 300-500 µg/dl
Severe - More than 500 µg/dl
46. Difficulties in interpretation of serum iron levels
Serum iron level reaches its peak at 4-6 hours
post ingestion, and time from ingestion is often
unknown.
Serum levels obtained more than 8-12 hours post
ingestion may not be useful because iron
redistributes into the tissues.
47. In case of slow release or enteric coated tablets,
levels should be repeated at six to eight hours as
absorption may be erratic.
Once Desferoxamine is started , it interferes with
standard assays and leads to falsely decreased
iron levels.
48. Is TIBC Useful In Diagnosis Of Acute Iron Toxicity?
🞇 TIBC should not be used to evaluate cases of iron
overdose. It measures iron bound to transferrin so, This
is because lab method used to measure it are
inaccurate in overdose and desferoxamine interferes
with its measurement
49. Prognostic investigations:
🞇 ABG (acidosis).
🞇 Glucose (hyperglycaemia).
🞇 Complete CBC.
🞇 Serum electrolytes, blood urea nitrogen (BUN), and glucose.
🞇 ALT , AST and bilirubin.
🞇 Prothrombin and partial thromboplastin time.
🞇 Clotting (reversible early coagulopathy and late coagulopathy
secondary to hepatic injury)
50. Parameters of Severity:
🞇 Anion gap metabolic acidosis is an important,
but nonspecific, predictor of iron toxicity.
🞇 Although leukocytosis and hyperglycemia are non
specific for acute iron toxicity , they are only associated
with serum iron levels greater than 300 mcg/dl.
Consequently , their absence doesn’t exclude acute iron
toxicity but their presence indicates severity of the case.
51. Treatment of Acute Iron Toxicity
Decontamination:
🞇Charcoal is of no benefit.
🞇Decontamination of choice is whole bowel
irrigation (WBI) with naso-gastric colonic lavage solution 30
ml/kg/hr until rectal effluent clear.
🞇WBI is contraindicated if there are signs of bowel obstruction or
hemorrhage.
53. Antidote:
🞇 Desferoxamine is a chelating agent which forms with iron
a water soluble complex.
🞇 Consider desferoxamine if:
Serum iron levels > 90 micromol/l.
Level 60- 90 micromol/l but tablets are visible on X ray .
Symptomatic patient e.g nausea, vomiting, hematemesis, fever, altered
consciousness, acidosis etc…
Worsening symptoms irrespective of ingested dose or serum iron level in
this case Do not wait for iron level start Desferroxamine without delay.
54. Dose :
It is given 15 mg/kg/hr I.V. maximum 35 mg/kg per hour, based on the
severity of clinical symptoms.
🞇 Desferoxamine - iron complex is renally excreted. If oliguria or anuria
develop, peritoneal dialysis or haemodialysis may become necessary to
remove desferroxamine.
55. When To Stop Desferoxamine?
🞇 There is no specific guidelines about duration of desferoxamine
treatment but Recommendations have used resolution of clinical
symptoms and normalization of lab investigations as the end point for
stopping therapy. This may lead to prolonged treatment with increase
the risk of lung toxicity.
56. 🞇 So , decision to stop desferoxamine therapy should be made according to
clinical toxicologist and/or regional PCC, guided by the patient's clinical
status.
Urgent stop of desferoxamine:
🞇 Desferoxamine should be stopped urgently if pulmonary toxicity appears ,
and should be used with caution if indications persist >24 hours.
57. Pitfalls In Management 0f Acute Iron Toxicity
🞇 Inadequate hydration of the patient.
🞇Failure to recognize patients in the latent phase.
🞇 Excessive reliance on the SIC, TIBC, or abdominal radiograph
in diagnosis and management decisions.
🞇 Inadequate desferoxamine dose.
🞇 Inappropriate discontinuation of desferroxamine.
🞇 Prolonged use of desferroxamine (more than 24 hours)
59. BARBITURATES
Non – Selective CNS depressants.
Derivatives of barbituric acid (2,4,6-trioxo hexa hydro pyramidine).
Popular sedative & hypnotics upto 1960’s.
Can produce effects ranging from
sedation and reduction of anxiety to
unconsciousness & death from respiratory & cardio vascular failure.
USES:
Sedative and hypnotic
Pre- operative sedation.
Treament of seizure disorders.
60. MECHANISM OF TOXIC EFFECTS
Direct CNS depressants.
Bind to GABA receptors.
Prolong the opening of chloride channel.
Inhibiting excitable cells of the CNS.
Potent inducer of hepatic drug- metabolizing CYP450 system,
so liable to cause drug interactions.
enzymes especially
Precipitate attacks of acute porphyria.
Tolerance & dependence occur.
61. ACUTE BARBITURATE POISONING
Leading cause of poisoning due to their ready availability.
Most of the cases are suicidal but some are due to error or ungraded exploration in
children.
Short acting barbiturates are more dangerous than long acting.
Shock & anorexia occur quickly.
Coma is more severe with short acting barbiturates.
62. SYMPTOMS
Stupor or coma, areflexia.
Peripheral circulatory collapse.
Weak & rapid pulse.
Cold clammy skin.
Slow or rapid & shallow breathing.
Pupils constricted & reacting to light initially but subsequently develops paralytic dilatation.
Atelectasis.
Pulmonary edema.
Bronchopneumonia
Acute renal shut down
64. HOSPITALIZATION:
Admitted to the hospital.
SUPPORT VITAL FUNCTIONS:
Consciousness.
Airway , breathing , circulation.
Blood pressure.
PREVENT FURTHER ABSORPTION:
Emesis.
Gastric lavage.
Activated charcoal & catharsis.
INCREASE ELIMINATION OF DRUG:
Forced diuresis.
Alkalinization of urine.
Prophylactic antibiotic.
Peritoneal dialysis.
Hemodialysis.
Hemoperfusion.
OTHER MEASURES:
Psychiatric after care.
65. BENZODIAZEPINES
Anxiolytics & hypnotic agents.
Wide therapeutic index.
Safest of all sedative drugs.
USES: Management of
Anxiety disorders
Seizure disorders
Insomnia
Movement disorders (adjunctive therapy).
Mania(adjunctive therapy).
66. MODE OF ACTION
Benzodiazepines
Stimulating GABA b receptors
Opening up the chloride ion channel in the receptor complex
↑se conductance of chloride ion across the nerve cell membrane Lowers the potential
difference between the interior & exterior of the cell
Blocking the ability of the cell to conduct nerve impulses
67. MECHANISM OF TOXICITY
Toxic symptoms-sedative action on the CNS.
Large doses-neuromuscular blockade .
Intravenous injection-peripheral vasodilation -fall in BP, shock.
↓se alveolar ventilation (↓se PO2 , ↑se PCO2 ).
Induce CO2 narcosis in persons with COPD.
Respiratory depressant effect with sedative drugs concomitantly taken.
Death occurred in persons who concurrently injected ethanol / CNS depressant.
IV dosing-hypotension & respiratory depression-death.
68. ACUTE POISONING OF BENZODIAZEPINES
Leading cause of poisoning due to their ready availability.
Most of the cases are suicidal but some are due to error or
ungraded exploration in children.
Short acting benzodiazepines are more dangerous than long acting.
Shock & anorexia occur quickly.
Coma is more severe with Anti anxiety benzodiazepines.
69. SYMPTOMS
MILD: Drowsiness , Ataxia , Weakness
MODERATE TO SEVERE :Vertigo , slurred speech, nystagmus, partial
ptosis, lethargy , hypotension, respiratory depression, coma (stage 1 & 2).
COMA 1 (Stage 1): Responsive to painful stimuli but not to verbal or tactile stimuli, no
disturbance in respiration or BP.
COMA 2 (Stage 2):Unconscious, not responsive to painful stimuli, no disturbance in
respiration or BP.
70. MANAGEMENT
LIFE SUPPORTIVE PROCEDURES & SYMPTOMATIC / SPECIFIC TREATMENT:
Airway , breathing & circulation.
Intravenous fluid administration.
Endotracheal intubation.
Assisted ventilation.
Supplemental oxygen.
DECONTAMINATION:
Stomach wash within 6-12 hrs.
Activated charcoal.
Emesis is contraindicated.
71. ANTIDOTE TREATMENT: FLUMAZENIL
Flumazenil –reversing the coma induced by benzodiazepines.
Mode of action – competitive antagonism.
Complete reversal of benzodiazepine effect with a total slow iv dose of 1mg.
Administered in a series of smaller doses beginning with 0.2 mg & progressively increasing by 0.1-
0.2 mg every minute until a cumulative total dose of 3.5 mg is reached.
Resedation occurs within ½ hr – 2 hrs.
75. Mostly Category C butAtenolol is category D
Atenolol crosses theplacental barrier
Studies show mothers taking Atenolol from 2nd trimester had babies that were toosmall
No studies on 1st trimesteror any other fetal harm Only Category B drugs are acebutolol, pindolol
&sotalol
Most beta blockers are excreted in breastmilk
So talk to your doctor if you have a little one on the way before taking beta blockers!
Sources:"Beta-AdrenergicBlockingAgents(Beta Blockers)." Facts andComparisons 2010. n. pag. WoltersKluwer Health,Inc. .
Web.12 Nov 2010.<http://online.factsandcomparisons.com>.
"Pregnancy&Chiropractic."chiropracticatthecomo.Web.13Nov2010.
<http://www.chiropracticatthecomo.com/Images/Pregnant.jpg>.
77. GI & METABOLIC ISSUES CNS & RENAL ISSUES RESPIRATORYISSUES
Mesenteric ischemia
Esophageal spasms
Hypoglycemia
Seizures
Coma or depressed
level of
consciousness
Renal failure
Apnea
Cyanosis
Respiratory depression
Bronchospasm
Source:Atenolol:Toxicology Data Network (TOXNET).National Libraryof Medicine :HazardousSubstancesData
Bank (HSDA),Web.15 Nov.2010.<http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~SpU8BZ:1>.
"Beta-AdrenergicBlockingAgents (Beta Blockers)."Facts andComparisons 2010. n. pag. WoltersKluwer Health,
Inc. .Web.12 Nov 2010.<http://online.factsandcomparisons.com>.
78. Symptoms may occur within 6
hours after ingestion and can be
as quick as 20 minutes
Onset of detectablesymptoms
will depend on formulations.
Extended release formulations
will take longer tomanifest
Source:Propranolol:Toxicology Data Network (TOXNET).National Libraryof Medicine
:HazardousSubstances Data Bank (HSDA),Web. 15 Nov. 2010.
<http://toxnet.nlm.nih.gov/cgi- bin/sis/search/f?./temp/~AGpJcu:1>.
"Beta Blockers-Top10 toxicities." UniversityofConneticut .Web.14 Nov2010.
<http://www.uconnem.org/toxicologyweb/cardiovascular.jpg>.
79. Vital Signs such Blood Pressure
Mental Status:is the patientalert?
ECG – Important to monitor for bradycardia, heart
failureor other severecardiac issues
Serum electrolytelevels will be low
Renal failurecan occur
Blood glucose levels will drop significantly
Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :Hazardous
Substances Data Bank (HSDA),Web.15 Nov.2010. <http://toxnet.nlm.nih.gov/cgi-
bin/sis/search/f?./temp/~AGpJcu:1>.
"VitalSignsCartoonsandComics." CartoonStock.Web. 14 Nov 2010.
<http://www.cartoonstock.com/lowres/hsc0561l.jpg>.
80. 1-2 HOURS AFTERINGESTION
Perform assessment of patient
condition
Determine serum glucose levels – if
hypoglycemic, treat with IV glucagon
Give activated charcoal to all patients
and gastric lavage if still within the 2
hour period
If is ER tablets they ingested, then do
whole bowel irrigation with
polyethylene glycol (PEG)
Source: "Beta-Adrenergic Blocking Agents (Beta Blockers)." Facts and Comparisons2010. n. pag. Wolters Kluwer Health,
Inc. . Web. 12 Nov 2010. <http://online.factsandcomparisons.com>.
"Polyethylene Glycol." Drugs.com. Web. 13 Nov 2010.<http://www.drugs.com/pro/polyethylene-glycol.html>.
Charcoal : used to help treat a drug overdose or a
poisoning, drugs and toxins can bind to it
81. chest radiography to prevent cardiac
failure
serum electrolytestoprevent potassium
buildup
Treatseizures with benzodiazepines, if they
are notworking, then treat with
barbiturates
Make sure activated charcoal is given
Benzodiazepines for Seizures!
82. Atenolol, acebutolol, sotalol, and nadolol are the only beta blockers
thatcan be removed by hemodialysis
Treatbronchospasm with beta agonists like albuterol
In patients who are still not responding to treatments mentioned
above, epinephrine(parenteral) may beneeded
Source: "Beta-AdrenergicBlockingAgents (Beta Blockers)." Facts and Comparisons 2010. n. pag. Wolters
Kluwer Health,Inc. .Web.12 Nov2010.
<http://online.factsandcomparisons.com>. "Epinephrine." MaineVille.Web.13 Nov2010.
<http://bdnimages.sprintout.com/uploads/large/127691247 3_8d68.jpg>.
83. Catecholamine agents– Epinephrine is most commonly used. However isoproterenol
and dopamine can be used as well
Phosphodiesterase inhibitors - Milrinone,aminophyllineand theophylline.Amrinone
has been shown to be good in dog trials
Insulin – High doses
Lipid Emulsion – IV,for propanolol overdose
Atropine – Most commonly used alternative agent but least effective. If patient does not
respond to a 1mg dose of atropine, you verify beta blocker toxicity (diagnosis tool)
Pacemakers– Controlcardiac pace in severe beta blocker induced bradycardia
intra-aortic balloon pump – to restoreperfusion and blood flow
Source: "Beta-AdrenergicBlockingAgents (Beta Blockers)." Facts and Comparisons 2010. n. pag. WoltersKluwer Health, Inc. .Web.12 Nov 2010. <http://online.factsandcomparisons.com>.
Atenolol: Toxicology Data Network (TOXNET). National Libraryof Medicine :HazardousSubstances Data Bank (HSDA),Web. 15 Nov.2010. <http://toxnet.nlm.nih.gov/cgi-
bin/sis/search/f?./temp/~SpU8BZ:1>.
84. IV fluids 500 mL bolusesup to 2L to raise blood pressure if the patient is hypotensive
1 to 2 mg lorazepam IV or another benzodiazepine for seizures
Propofol can be usedalong with thelorazepam
If patient has QRS widening and ventricular dysrhythmias, then treat with IV sodium
bicarbonate 1 to 2 mEq/kg IV bolus starting dose,titrate to blood pH 7.45 to7.55
Use lidocaine if sodium bicarb is notworking
Liquid ActivatedCharcoal: 1 g/kg PO up to 50-100 grams. For children up to 15-30 grams
Source: Propranolol: Toxicology Data Network (TOXNET). National Library of Medicine :HazardousSubstances Data Bank (HSDA),Web. 15 Nov.2010. <http://toxnet.nlm.nih.gov/cgi-
bin/sis/search/f?./temp/~AGpJcu:1>.
Sharma,Adhi."Beta BlockerToxicity."EmedicinefromWebMD. WebMD,03 NOV 2010.Web.15 Nov2010.
<http://emedicine.medscape.com/article/813342-overview>.
85. Glucagon: Initial dosing is 5 to 15 mg
slow IV push with an infusion rate of
5 to 15 mg/hour.
Phosphodiesterase inhibitor
(Inamrinone) - 1 mg/kg bolus then 3
to 6 mcg/kg/minute
Calcium for beta blocker
(propranolol or atenolol) &
verapamil overdose- calcium
chloride 0.2 mL/kg or calcium
gluconate 0.6 mL/kg intravenously
Dextrose bolus is another option.
Giveto patient with blood glucose
of less than 250 mg/dL
- Adults: 25 to 50 mL dextrose 50%
-Children: 0.25 g/kg dextrose 25%
87. Patient Case
4/15/16
• A 64 y/o male was transported from Massena, NY to UVM MC ED after
ingesting fifty 5mg amlodipine tablets
• Per family, patient has been depressed and suicidal for several
days
88. AMLODIPINE
THE BASICS
Class DHP-type calcium channel blocker
MOA Directly inhibits vascular and myocardial L-type calcium
channels
Side effects Common: edema, dizziness, flushing, palpitations Other: fatigue,
nausea, abdominal pain, somnolence
Therapeutic range 2.5 to 10 mg daily
Max dose 10 mg daily
89. Why Is This Important?
• Calcium…
• Initiates excitation-contraction coupling (muscles)
• SA node depolarization (heart)
• Maintains smooth muscle tone (vascular and GI
system)
• Reduces insulin secretion (pancreas)
90.
91. Methods of Toxicity
• Calcium Channel Blockers…
• Initiates excitation-contraction coupling (muscles)
• inotropy
• SA node depolarization (heart)
• chronotropy
• Maintains smooth muscle tone (vascular and GI system)
• vasodilation
• Reduces insulin secretion (pancreas)
• blood glucose
• glucose utilization by the heart
92. Methods of Toxicity
• Calcium Channel Blockers…
• Initiates excitation-contraction coupling (muscles)
• inotropy **non-DHP
• SA node depolarization (heart)
• chronotropy **non-DHP
• Maintains smooth muscle tone (vascular and GI system)
• vasodilation **DHP
• Reduces insulin secretion (pancreas)
• blood glucose
• glucose utilization by the heart
93. Early Symptoms
• Fatigue, dizziness and lightheadedness
• Severe poisoning: syncope, altered mental status, coma, sudden death
• DHP CCBs:
• Primarily peripheral vasodilation reflex tachycardia
• Loss of selectivity during severe poisoning
bradycardia
95. Interventions
• General
• Goal: supportive
• Cardiogenic shock
• Goal: improve contractility and bradycardia
• Vasodilatory shock
• Goal: improve vascular tone
96. Initial
• GI decontamination
• Immediate release: activated charcoal
• Within 4 hours of ingestion
• Extended release: whole bowel irrigation
• Only if asymptomatic
• Airway and respiratory support
• IV isotonic crystalloid
• 1-2 L max
98. Atropine
Indication MOA Effects Dose Adverse
Effects
Symptomatic
bradycardia
ACH-
mediated
bradycardia
HR
(may not be
significant or
persistent)
0.5-1 mg IV
q2-3 minutes (max
3 mg)
Anti-ACH
effects
Treatment failure should be anticipated with severe poisoning
99. Glucagon
Indication MOA Effects Dose Adverse
Effects
Cardiogenic
shock
Ca2+ channel
activation (via
adenylate cyclase
and cAMP)
HR 5 mg IV bolus (can
repeat x 2 every 10
min)
N/V
Hyperglycemia
100. Calcium
Indication MOA Effects Dose Adverse
Effects
Hypotension and
bradycardia
Ca2+
concentration
gradient across
cellular membrane
BP, CO and
vascular tone
Loading dose:
13-25 mEq Ca2+
Hypercalcemia
Hypophosphat
emia
Infusion:
0.5 mEq
Ca2+/kg/hr
ECG changes
Tissue injury
with
extravasation
Effects may not last and may not be significant in severe poisoning
106. Vasopressin
Indication MOA Effects Dose Adverse
Effects
Vasodilatory
shock
Vasoconstrictio n
via:
Vascular V1
receptor
activation
ATP-activated
K+ channels
nitric oxide
Adrenergic
potentiation
BP
systemic
vascular
resistance
Titrate to effect
Max 0.04
units/min
CO
Limb ischemia
107. Third-Line
• Intravenous fat emulsion (refractory shock or cardiac arrest)
• Methylene blue (refractory shock)
• Phosphodiesterase inhibitors
108. Intravenous Lipid Emulsion
Indication MOA Effects Dose Adverse
Effects
Refractory
cardiogenic or
vasodilatory shock
Muscle
contraction
Energy
Active drug
BP, HR and
perfusion
Loading dose: 1-1.5
mL/kg of
20% ILE
Infusion:
0.25-0.5
ml/kg/min of 20%
ILE
Blood
viscosity
Pancreatitis
Noncardiogeni c
pulmonary edema
109. n
Intravenous Lipid Emulsion
Three proposed mechanisms:
• Ca2+ channel activation
• intracellular metabolism
• “Lipid Sink”
• Inactivation via sequestratio
• Dependent on lipophilicity
• Amlodipine LogP = 3.72
• Verapamil LogP = 4.91
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110. Methylene Blue
Indication MOA Effects Adverse Effects
Refractory
vasodilatory
shock
Nitric oxide: (nitric
oxide-cGMP pathway,
scavenges and inhibits
synthesis)
BP
vasopressor
dosing
Blue discoloration
(skin, secretions)
Hemolysis
Methemoglobinemia
Serotonin syndrome
(inhibits MAO-A)
111. Phosphodiesterase Inhibitors
Indication MOA Effects Agents Adverse
Effects
Cardiogenic
shock
Ca2+ channel
activation (via
adenylate cyclase
and cAMP)
HR and CO Milrinone
Inamrinone
Enoximone
HoTN
Vasodilation
Not readily available and may exacerbate HoTN
113. sulfonylureas
• Oral hypoglycemic agents commonly are referred to as sulfonylureas, a class
of compounds.
• Sulfonylurea compounds are among the most widely prescribed medications
in the world.
• The drugs are frequently used to treat patients with type II diabetes.
• Wide availability of these medications increases potential for either
intentional or unintentional overdose in pediatric and adult populations
114. • other agents besides sulfonylureas are used to treat type II diabetes, including
biguanides, alpha-glucosidase inhibitors, and troglitazone. Metformin
(Glucophage in the United States) is one such agent.
• Even in excessive dosage, these agents do not decrease serum glucose below
euglycemia; consequently, they are referred to appropriately as
antihyperglycemic agents rather than hypoglycemic agent
115. • A single tablet of sulfonylurea has been reported to produce
hypoglycemia in a child.
• Glipizide has been reported to produce hypoglycemia within 5 minutes of ingestion in an
adult.
• A child can become hypoglycemic after ingestion of 1 glipizide 5-mg tablet.
• Patients usually become symptomatic within 2 hours of ingestion. Symptoms of
hypoglycemia may be delayed if food is taken with the oral hypoglycemic agents. Symptoms
may include the following:
• Lethargy
• Confusion
• Irritability
• Unresponsiveness
• Dizziness
• Headache
• Blurred vision
• Psychotic behavior
• Emesis
• Delirium
• Feeding difficulties
neurologic
• Diaphoresis
• Tachycardia
• Tachypnea
• Transient
deficit
• Seizure
• Cyanosis
• Coma
• Hypothermia
116. Work up
• Fingerstick and/or serum glucose test to detect hypoglycemia (If hypoglycemia does
not occur within the first 2-4 hours after suspected ingestion/overdose, then other
laboratory tests are unnecessary.)
• Baseline CBC count (in symptomatic patients)
• Baseline electrolytes, especially potassium (in symptomatic patients)
• Serum aspirin and acetaminophen concentrations, and urine toxicological screening,
if intentional ingestion/suicide attempt is suspected
• Pregnancy test, if indicated
• Ethanol level, if indicated
117. Medical care
• intravenous administration of glucose rapidly resolves the effects of hypoglycemia.
Its onset is quicker than oral administration of sugar, and it is safer in patients with a
depressed mental status who should not take anything by mouth for fear of
aspiration.
• Glucagon is helpful and can be administered intravenously, intramuscularly, or
subcutaneously. Glucagon is particularly useful in the intramuscular mode when
intravenous access cannot be obtained immediately.
• one study suggest that because accidental ingestion of sulfonylurea results in delayed
and often prolonged hypoglycemia, admission for at least 16 hours is
recommended, with frequent glucose monitoring.
118. • If a patient is lethargic, then oxygen, continuous cardiac monitoring, and
pulse oximeter are indicated. Until the patient totally regains mental status, do
not administer anything by mouth.
• Depending on the amount of the drug and its half-life, patients may require
intravenous glucose administration for anywhere from several hours to
several days. If patients do not respond to continuous glucose administration
with supplemental boluses, then octreotide or diazoxide can be administered.
119. • Ipecac is not recommended because of the possibility of aspiration in patients with a
depressed mental status.
• Administer activated charcoal as soon as possible, preferably within 1 hour of
ingestion; however, most unintentional pediatric exposure results in ingestion of 1 or 2
tablets of sulfonylureas. No data indicate that gastric lavage or administration of
activated charcoal has any benefit in these cases.
• Multiple doses of activated charcoal have been suggested in patients with glipizide
overdose because this hypoglycemic agent has an enterohepatic circulation.
• Hemodialysis is not indicated because most sulfonylureas have high protein binding.
120. metformin in the acute
overdose setting
• without hypoglycemia. When lactic acidosis occurs in patients using therapeutic
doses of metformin, it is considered life- threatening because reported case series
demonstrate a death rate of approximately 50%.
• Hypoglycemia was only seen in patients with concurrent ingestions of insulin or
sulfonylureas.
• Other symptoms reported in scant case reports include lethargy
and disseminated intravascular coagulation (DIC).
• Patients who are not diabetic presented with symptoms of GI complaints, headache,
and dizziness.
• A single case series of children with reports of accidental metformin exposure found
no significant health risk of hypoglycemia and no evidence of lactic acidosis.
121. • The mechanism thought related to metformin induced lactic acidosis includes
decreased gluconeogenesis from alanine, pyruvate, and lactate leading to
lactate accumulation.
• The risk of metformin associated lactic acidosis is increased with concurrent
renal insufficiency and therefore the drug should not be used in these patients.
• Lactic acidosis, associated with biguanide therapy, is treated with sodium
bicarbonate and hemodialysis, resulting in rapid improvements in acid-base
status and removal of metformin from the blood.
122. • There is little information regarding overdose with the thiolidinediones.
Overdose information is derived from adverse effects at therapeutic levels.
• Although infrequently reported, hypoglycemia can occur,
especially when used in a poly-drug regimen.
• Reports of hepatotoxicity occur after therapeutic troglitazone therapy, but
long-term studies especially on the recently released agents are lacking.
Are the
thiolidinediones such as troglitazone, piaglitazone,
and rosiglitazone toxic?
