12 Overdose Flashcards
Drug Overdose
- The ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced;
- Accidentally: e.g. children – e.g. paracetamol;
- Deliberately: e.g. suicide, or drug abuse (next lecture)
- The drugs most frequently used for intentional self-poisoning are benzodiazepines, analgesics and antidepressants, often taken with alcohol;
Risks of drug overdose - Drug with Risk
- narrow therapeutic window (digoxin, teophylline)
- steep dose-response curve (warfarin, sulhonylurea der.)
- enzyme inhibitors (ketoconazole, erythromycin)
- enzyme inducers (rifampicin, carbamazepine)
- high toxic potential (aminoglycosides)
Risks of drug overdose - Patient with Risk
- polymorbidity
- polypharmacy
- treatment lasting long time
- chronic diseases e.g. disorders of elimination functions
- abusus
- non-compliance • self-treatment
- simultaneous ordination of more drugs by different physicians
Therapeutic Index =
Therapeutic Index =
Dose causing toxicity/ Dose providing efficacy
Drugs with Narrow Therapeutic Window
Aminoglycoside antibiotics - gentamicin, tobramycin
Anticoagulants - warfarin, heparins, high protein bound
Aspirin (salicylate derivatives),
high protein bound
Carbamazepine
enzyme inducer
Conjugated / Esterified estrogens
OC pills, enzyme inducers
Cyclosporine
immunosupressant
Digoxin
cardiac stimulant/tonic
Hypoglycemic agents
Levothyroxine
Lithium
Phenytoin
nonlinear pharmacokinetics
Procainamide - heart arrhythmia
Quinidine - heart arrhythmia
Theophylline (aminophylline)
Tricyclic antidepressants
Valproic acid
Principles of treating overdose
- Overdose
- Immediate measures Evaluation,
Remove contact, ABC, history, evidence - Supportive measures
Cardiac/respiratory arrest Hypotension, Arrhythmia Convulsions, Renal or Hepatic failure, temperature - Prevent Absorption
(Emesis), Activated charcoal, Gastric Aspiration/lavage - Elimination
Alkaline diuresis (sodium bicarb.)
Acid diuresis (ammonium chloride)
Haemodialysis - Antidotes
- Psychiatric assessment
Supportive care
- ABC (airway, breathing, circulation)
- Protect airway
- Vital signs, mental status, and pupil size
- Pulse oximetry, cardiac monitoring, ECG
- Intravenousaccess
- cervical immobilization if suspect trauma
- Rule out hypoglycaemia
Preventing absorption
Gastric lavage
- Flexible tube is inserted through the nose into the stomach
- Stomach contents are then suctioned via the tube
- A solution of saline is injected into the tube
- Not in unconscious patient unless intubated (risk aspiration)
Preventing absorption
Induced Vomiting
• Not routinely recommended, due to risk of aspiration
Preventing absorption Activated charcoal
- Adsorbs toxic substances or irritants, inhibiting GI absorption
- Oral: 25-100 g as a single dose
- repetitive doses useful to enhance the elimination of certain drugs (eg, theophylline, phenobarbital, carbamazepine, aspirin)
- However, charcoal does not absorb petroleum distillates, inorganic acid and alkali, alcohol, metal ions, cyanide, lithium.
Elimination of poisons
Renal elimination
• Medication to stimulate urination or defecation may be given to try to flush the excess drug out of the body faster.
Elimination of poisons
Forced alkaline diuresis
- Infusion of large amount of NS+NAHCO3
- Used to eliminate acidic drug that mainly excreted by the kidney eg salicylates
- Serious fluid and electrolytes disturbance may occur
Elimination of poisons
Hemodialysis or haemoperfusion
- Reserved for severe poisoning
- Drug should be dialyzable i.e. protein bound with low volume of distribution
- may also be used temporarily or as long term if the kidneys are damaged due to the overdose.
Antidotes
Agents with a specific action against the activity or effect of drugs involved in poisoning cases.
Antidotes mechanisms and
examples
Pharmacological antagonists
Naloxone (opiate poisoning) Ethanol (methanol poisoning)
Enhance physiological function to compensate
Physostigmine (belladona alkaloid poisoning)
Restore active site of drug target
Pralidoxime (poisoning by organophosphates, e.g. pesticides, war gas)
Bypass block
Glucagon (beta-blocker poisoning)
Sequester poison
Digibind (digoxin poisoning
Speed up excretion
Chloride is used as an antidote for bromide / iodide overdoes.
Clinical features
• Stage I (0.5 to 24 hours)
No symptoms; nausea & vomiting (N&V); malaise
• Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
Elevations of prothrombin time (PT) and total bilirubin
Right upper quadrant pain, with liver enlargement and tenderness Oliguria and renal function abnormalities
• Stage III (72 to 96 hours)
Jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes, hyperammonemia, and a bleeding diathesis hypoglycemia, lactic acidosis, renal failure 25%, death
• Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4
Paracetamol overdose management
<4 hour : Activated charcoal
May reduce absorption by 50 to 90 percent Single oral dose of one gram per kilogram
<8 hour : acetylcysteine (antidote) a glutathione precursor Limits the formation and accumulation of NAPQI
<24 hour: methionine p.o.
Protect liver from damage
>24 hours: specialist advice for liver transplantation
Liver transplantation is life-saving for fulminant hepatic necrosis The indications for liver transplantation are:
1 - Acidosis (pH < 7.3)
2 – Prothrombin time (PT) > 100 sec
3 - Creatinine > 300 mcg/l,
4 - Grade 3 encephalopathy (or worse)
NAPQI
toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol. It is normally produced only in small amounts, and then almost immediately detoxified in the liver.
Aspirin
- Antiplatelet therapy
- Inhibition of COX-1 and COX-2
- Interference with metabolism
i. Prevents the formation of ATP and promotes the formation of lactate and pyruvate
ii. Inhibits the Krebs cycle enzymes, encouraging lipid metabolism and ketogenisis
iii. Inhibition of amino acid metabolism. - Activation of the Respiratory Center in the Medulla
Aspirin Overdoes
-Fatal intoxication can occur after the ingestion of 10 to 30 g by adults and as little as 3 g by children;
-Metabolic acidosis
-An acidic pH promotes the movement of
salicylate into the tissues
-Respiratory alkalosis
-Electrolyte imbalance
Increased renal excretion of bicarbonate, Na+, K+ follow Increased pulmonary insensible losses
Vomiting
Hyperthermia causing skin insensible losses
Management
• The use of activated charcoal has shown to reduce the amount of active salicylate by 50-80% in the initial presentation,
– in vitro studies suggest that each gram of activated charcoal can absorb approx. 550 mg of ASA
– A ratio of 10:1 charcoal to salicylate has the maximum effectiveness
• Multiple doses of activated charcoal appears to be superior to single doses although current data is presently insufficient
• Fluid replacement is very important in the management of salicylate toxicity
– major fluid losses through tachypnea, vomiting, hypermetabolic state, and insensible perspiration
Most important Management
• The most important management is through urine alkalinization with sodium bicarbonate, resulting in enhanced excretion of ionized acid form of salicylate
– Alkalinization can be achieved with a bolus of 1-2 mEq/kg, followed by an IV infusion of 3 ampules of sodium bicarbonate in 1 L of D5% to run at 1.5-2 times maintenance fluid range
• Alkalinizing the urine from a pH of 5 to 8 increased renal clearance from 1.3 to 100 ml/min
• Urine pH must be maintained at 7.5-8.0 and hypokalemia must be corrected
Management -Indications of hemodialysis
• Renal failure
• Congestive heart failure
• 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 the absence of the above)
Opiates overdose
• Opioids bind to specific opioid receptors in the CNS;
• Characteristic of opiates overdoes: – respiratory depression
breathing slows down, sometimes to a stop – pinpoint pupils
an important diagnostic feature in opioid poisoning – decreased level of consciousness
– hypotension and bradycardia
heart rate slows down, sometimes to a stop
blue lips, nails (due to insufficient oxygen in the blood)
• Morphine / Heroin overdoses are the most common single cause of death from drug overdose, account
for 25% of the total;
Opiates overdose management
• Antidote – naloxone,
a competitive antagonist at opioid m receptors
• I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2 mg every 2-3 minutes as needed
• Elimination half-life of naloxone is only 60 to 90 minutes
• Repeated administration/infusion may be necessary
• S/E: BP changes; arrhythmias; seizures; withdrawal
Pesticides
Pesticides (and nerve (war) gas) are organophosphate
– irreversible anticholinesterases (AChE);
- Nicotinic signs: Twitching, Fasciculations, Muscle weakness, Cyanosis, Elevated BP
- Muscarinic signs: Bronchoconstriction, Increase secretion, Sweating, GI, Meiosis
- CNS signs: Anxiety Restlessness, Confusion, Headache
Management of pesticides
• Supportive care – clear airway (why ?);
• AChE regenerator, known as oxime agents, which can
hydrolyze the phosphorylated AChE;
• Pralidoxime (antidote) i.v.1-2 g for over 15-30 min. and for several days in severe poisoning;
• must be used quickly after exposure before pesticide conjugate
“ages” and becomes unreactive;
• It has positive charge and does not enter the CNS, can’t
reversing the effects of organophosphate poisoning on CNS;
• Simultaneous use of atropine is required to control muscarinic
excess.
• Pretreatment with reversible inhibitors (e.g. pyridostigmine or physostigmine), to protect against excessive AChE inhibition
when possibly lethal poisoning is anticipated,25 e.g., peasants, soldiers (chemical warfare);
The principles of treating overdose
Evaluation
Supportive
Prevent absorption Elimination
Antidotes
Examples of drug overdoes management
Paracetamol
Aspirin
Opiates
Organophosphate pesticides
