Lecture 2 Flashcards
Decontamination, Elimination, Antidotes
If symptoms have already occured?
Means absorption has already occurred and its efficacy decreases with time
What is the concept of activated charcoal>?
Toxicant-Ac complex is not systemically abosrbed, toxicant and it is excreted
What is activated charcoals adsorptivity attributed to?
Highly porous structure
Adsorption of drugs and toxins occurs through ___
weak intermolecular forces
Activated charcoal becomes ____ effective with use
less
___ and ___ compound bind more avidly than ___ ___ ___
Non ionized, organic compounds, dissociated, inorganic ones
What agents are adsorbed by AC? (10)
What medications are NOT adsorbed by AC? (9)
What is the typical dosing of AC in <1
1g/kg
What is the dosing of AC in 1-12 yo
25-50g
What is the dosing of AC in >12 yo
25-100
When can we provide AC in context of the poison absorption
Within 1 hour of ingestion
If a patient has ingested a potentially toxic amount of poison up to 1 hour following ingestion
Insufficient data to support or exclude the use of AC more than 1 hour passed since ingestion
What are some other dosage forms of AC we can provide?
What are some factors that increase AC appropriateness?
Alert, cooperative, and adsorb
What are the contraindications of AC?
Toxicant known not to adsorb AC
Unprotected airway
Ingestion of hydrocarbon
Risk of GI perf
Endoscopy required
Examples of hydrocarbons
What is the risk of GI perforation products?
What is emesis?
Vomitting
What are some complications of AC?
Vomitting
Constipation/diarrhea.
Pulmonary aspiration
Black stool
When should we reserve gastric lavage for?
What is a whole bowel irrigation?
Cleanses bowel with large amounts of peg solutions to minimize drug absorption and expel intraluminal contents
When is WBI an option?
Whole bowerl irrigation: Expediting the gastrointestinal luminal clearance, drug smugglers lololol
There is a ___ of WBI being succesful in body packers
98%
WBI ___ lithium concentration
Decreases
Are there an established indications of WBI?
No
What is the theoretical benefit of drug
What are the contraindications of whole bowel irrigation
What are some of the complications of PEG-ES? (5 main points)
What are the other methods of decontamination? (3)
Surgery, kayexalate for lithium
Cholestyramine (Dont need to know the names)
A Vd of ___ is considered large
> 1 L/Kg, only a small portion of total dose is in the plasma
What are the intracorporeal elimination methods?
Multiple dose activated charcoal
What are the Extracorporeal? elimination methods?
Hemodialysis, Hemofiltration. Hemoperfusion
MDAC ___ absorption to the tissues when large amount of xenobiotics are ingested and dissolution is delayed OR when reabsorption can be prevented by lowering concentration of free toxic substance in the intestinal lumen
Decreases
For the MDAC how is dosing determined?
The amount and dosage form of xenobiotic
MDAC is enhanced in (5)
Carbamazepine. Dapsone, phenobarbital, quinine, theophyline
What are the main CI of MDAC?
Multi dose activated charcoal is CI in
What are the complicaitons of MDAC?
Reduciton of therapeutically used xenobiotics as the therapeutic xenobiotic may bind to the AC
What is the indication of MDAC?
Drugs with long t1/2 small Vd and those that undergo enterhepatic recirculation
What is hemodialysis?
uses diffusion through a concentration gradient
What is hemofiltration?
Uses convection through a pressure gradient
(Helps to remove large molecules)
What is hemoperfusion?
Blood passes through adsorbent substance (large molecule, plasma removed and treated)
What is Hemodiafiltraiton?
Combines hemodialysis and hemofiltration
What is the difference between hemodialysis and hemofiltraiton?
What is hemoperfusion?
BLood passes through a cartridge containing sorbet (AC)
Ionized drugs ____ cross the lipid bilayer
cannot
Alkalization of the urine helps clear weak acids by trapping the xenobiotic in the tubular lumen’s and ________ it to be passively reabsorbed into the blood stream
not allowing
Alkalinizaiton by
Sodium bicarbonate
What are the CI of alkalinzation?
Renal failure, heart failure
What are the complications of alkalinization?
What are the indications of alkalinization?
Moderate to severe salicylate poisoning who do not meet the criteria for hemodialysis
What are the 4 types of antidotes?
Receptor antagonists
Chemical/Chelator
Dispositional
Unclassified
What are some receptor antagonist exmaples?
Atropine, Vitamin K
What are some examples of chemical Chelator?
Forms compounds of lesser toxicity that is removed
What is dispositional?
Ethanol, fomepizole
What is atropine?
Acetyl cholinesterase inhibitors
What is the general principle of antropine?
Prevents breakdown of acetylcholine thereby increasing acetylcholine available to stimulate cholinergic receptors
Atropine pathway
Parasympthathetic blockers
Decreases salivia
Atropine is reversed by?
Physostigmine
What is deferoxamine used for?
When serum levels of iron is >90umol/L
How does Deferoxamine work?
Acts as a chelator and binds free iron to for ferrixoamine which is renally excreeted
What is the complications of Deferoxamine?
What is Digifab?
DIgoxine-specific antibody fragments
How does Digoxin work?/
Blocks NA/K atpase pump which allows for calcium to accumulate and allow for better contraction
What is Digifab?
Antibody fragment
Each vial of digifab binds
0.5mg
Average # of vials of digifab needed for acute toxicity is
10
Average # of vials needed for chronic toxicity is (Digifab)
6
What are the complications of digifab?
Inotropic effect of digoxin decreases may need to be treated with inotropes or vasodilators.
What is Idarucizumab/praxbind
Reverses dabigatran
What is praxbind>?
Idarucizumab
Reversal of anticoagulant effects of dabigatran can result in
life-threatening bleeding
WHat is the precautions of idarucizumab>
Contains 4g of sorbitol which can have serious adverse effects
Toxic alcohols
Ethylene glycol, methanol, isopropranol
Lethal dose of ethylene glycol is?
1.4mL/kg
Lethal dose of methanol?
1-2ml/Kg
ethylene glycol and methanol are not toxic
Kinda true, the metabolites are what are toxic
Why do we use ethanol for ethylene glycol and methanol overdose?
So they are not metabolized and ethanol is metabolized
Ethanol has a ___ affinity for alcohol dehydrogenase
15.5x
Good slide to review
Ethanol has ___ more affinity than ethylene glycol
67x
What enzymes metabolize methanol?
Alcohol deydrogenase
Aldehyde dehydrogenase
What enzymes metabolize ethylene glycol
Aldehyde dehydrogenase
Lactate dehydroganse
What is the toxic compound sof ethylene glycol>
Glycoaldehyde, glycolic acid, oxalic acid
What are the toxic metabolites or methanol?
Formaldehyde, formic acid
Review
Why do we want to give hemodialysis for patients once alcohol dehydrogenase?
The relative affinity of fomeprizole for human ADH is ___ greater than that of methanol and ethylene glycol and ___ than that of ethanol
80 000, 8000