Term
Steps in the Clinical Treatment of Drug Overdose |
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Definition
•Patient stabilization
•Clinical evaluation.
•Prevention of drug absorption.
•Enhancement of drug elimination.
•Administration of antidote (when applicable).
•Supportive care.
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Term
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Definition
•Establishment of airway
•O2 if needed
•Maintenance of circulation (volume replacement).
–Administer lactated Ringer or isotonic sodium chloride solution for volume expansion at 10-20 cc/kg/h until a 1-1.5-cc/kg/h urine flow is established.
–Correction of fluid deficits and enhancement of excretion and elimination
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Term
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Definition
•Useful in predicting clinical outcome and devising treatment regimens.
•Only apply to one single, acute dose. Does not apply to chronic dosing. Also not terribly useful for time-release formulations.
•For acetaminophen, plasma samples should be taken at least 4 h following the dose to ensure peak plasma concentration has been reached.
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Term
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Definition
•Important in evaluating poisoning when immediate, specific clinical tests are not available.
•Can themselves be used for rough diagnosis.
–Ex.) Metabolic acidosis with anion gap > 12:
•Limited number of culprits.
–Ex.) Elevated osmol gap (> 10 mOsm) suggests the presence of another osmotically active substance.
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Term
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Definition
Elevated anion-gap acidosis is usually caused by an increase
in the presence of unmeasured acid ions, for example, formate
(for methanol poisoning). The difference gives the number of
unmeasured ions.
Definition of metabolic acidosis: Disturbance of the body’s
acid-base balance.
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Term
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Definition
Measured serum osmolarity (mOsm) – calculated
serum osmolality.
Where serum osmolality =
2 X [Na] meq/L + [Glucose] mg/dL + [BUN] mg/dL
18 2.8
•Osmolarity is measured by serum freezing point
depression.
• Definition of osmolarity: number of osmotically
active particles/L of solution. Basically, it’s the
number of dissolved particles.
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Term
Differential Diagnosis by Acidosis or Elevated Anion Gap |
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Definition
•Alcohol (ethanol ketoacidosis)
•Toluene
•Methanol
•Uremia
•Diabetic ketoacidosis
•Paraldehyde
•Iron
•Lactic acid
•Ethylene glycol
•Salicylate
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Term
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Definition
-Inhibition of
Absorption
-Enhancement of
Elimination
-Antidotes
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Term
Methods of Treatment I:
Prevention of Further Absorption |
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Definition
- Gastric Lavage
-Induction of Emesis
- Activated Charcoal |
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Term
Activated charcoal, continued. |
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Definition
•Use has increased over the last 20 years.
•Charcoal slurry is administered by orogastric tube.
•Adsorbs organics.
•Charcoal is “activated” by superheated steam – increases number of pores.
•Does not adsorb small polar compounds like ethanol or ethylene glycol (antifreeze) very well.
•Many treatment centers are beginning to favor its use over emesis and gastric lavage following a large number of clinical trials showing its superiority.
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Term
Methods of Treatment II.
Enhancement of Elimination |
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Definition
•Alkalinization of the urine
•Hemodialysis
•Hemoperfusion
•Serial oral activated charcoal
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Term
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Definition
•Enhances the elimination of weak acids (such as aspirin).
•Increases the pH of urinary filtrate (so that it is ionized) to prevent reabsorption by the tubules.
•Ion trapping: Trapping the agent in the filtrate by forcing the majority of the compound to exist in its ionized form. Ions are not reabsorbed and are instead excreted.
•Accomplished by adding sterile sodium bicarbonate with 5% dextrose for IV administration and titrating the urine up to pH 7.5 or 8.
•PCP overdose is one of the rare cases where acidification is useful. Acidification can lead to acid-base and electrolyte disturbances that induce acute renal failure.
•
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Term
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Definition
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•Removal of a toxic substance by equilibration with dialysate across a semipermeable membrane.
•To be effective, toxicant must be water-soluble and of low molecular weight.
•Must exhibit low protein binding and volume of distribution.
CANT GET DIGOXIN BECAUSE IT IS NOT CIRCULATED IN BLOOD
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Term
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Definition
•Blood is pumped through a perfusion cartridge filled with charcoal or resin.
•Criteria for efficient hemoperfusion:
–Efficient adsorption to charcoal
–Lipid soluble and/or high MW.
–Protein binding does not interfere.
•Risk: hypocalcemia, thrombocytopenia, leukopenia.
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Term
MDAC – Multiple Dose Activated Charcoal |
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Definition
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•Serial administration (every 2 – 4 h) of activated charcoal.
–Increases systemic clearance
–Increases nonrenal clearance
–Blocks enteroheptic circulation
–Serves as a sink in the gut for toxin
•Toxins that favor MDAC
–Significant enterohepatic circulation and bioactivation.
–Prolonged plasma half-life
–Small Vd
–Small amount of protein binding
–pKa that maximizes transport across cell membranes
–Sustained release tablets
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Term
Antidote Treatment: Methanol |
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Definition
•Main component of some windshield wiper fluids
•Clinical signs: Elevated anion gap and osmol gap.
•Treatment: IV sodium bicarbonate and hemodialysis.
•Methanol is bioactivated:
Methanol formaldehyde formic
acid
•Agents which inhibit ADH (4-methylpyrazole) or saturate the enzyme (sterile solutions of ethanol) are used as therapies. Note: 4-MP (also referred to as fomepizole) and ethanol infusion can also be used to treat ethylene glycol poisoning.
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Term
Treatment of Metabolic Acidosis
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Definition
•Treat the metabolic acidosis.
•Inhibit metabolism using ethanol or fomepizole.
–Fomepizole, an inhibitor of ADH, does not induce CNS depression or hypoglycemia, and plasma levels are easier to maintain than ethanol.
•Hemodialysis.
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Term
Antidote Treatment for Acetaminophen
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Definition
•Clinical presentation is confusing. Difficult to estimate time of ingestion.
•Waiting for clinical symptoms is an inadequate strategy. Presentation of symptoms may be delayed.
•By comparison to the nomogram, plasma APAP concentration can help determine whether N-acetylcysteine (NAC) therapy is required.
•Support therapy: activated charcoal and gastric lavage (for very recent ingestion).
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