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Flashcards in topic 24 Deck (25):

What can happen when multiple tablets are ingested at the same time? What is a dangerous example of this?

Adherent masses of tablets “concretions”

Reduced surface area for dissolution

Prolonged absorption from huge drug

Beware aspirin, meprobamate


What can anticholinergic or narcotic drugs do to adsorption?

 Agents with anticholinergic or narcotic
effect may slow GI motility

Unabsorbed drug trapped in quiet gut

When gut recovers, absorption resumes

Patient relapses; cyclic effect


What are some drugs that typically display michaelis menten kinetics? Why are MM patterns more common at higher doses? What is the result?

 Saturation kinetics are unusual clinically
because doses are so small

 BUT, metabolism of higher doses may exhibit
a saturation point

 Common agents with MM at typical doses:
ethanol, aspirin, phenytoin

 Slower decline of blood concentrations

 Don’t count on a known “half-life” derived
from therapeutic dosing


What are 5 therapeutic interventions used to augment clearance?

 Therapeutic interventions used to
increase the clearance

v Adsorption to activated charcoal

v Chelation

v Specific antibody fragments

v Enhanced endogenous clearance

v Extracorporeal removal


What are 2 things that can be done to enhance endogenous clearance via the kidney? What are two things that shouldn't be done? What can they be used to clear?

Use adequate or robust hydration to maintain renal bloodflow and glomerular filtration.

Use the concept of ion trapping for acids such as salicylic acid or 2-4-D by alkalinizing urine using IV sodium bicarb which will cause the toxin to be more unionized in tubule cells making it more likely to be excreted.

Don't force Diuresis!

Don't acidify urine to help excrete weakly basic toxins. Its dangerous.


What are 3 types of extracorporeal removal? How does the concept work in general?

 Blood is diverted through an apparatus
which removes toxin & returns blood to circulation

• Hemodialysis (most common, still rare)

• Hemoperfusion

• Hemofiltration


How common is hemodialysis used for poison patients? What are five toxins that its indicated for?

 HD benefits only a small percentage of
poisoned patients

 Considered for poisoning by

• Methanol

• Ethylene glycol

• Lithium

• Theophylline

• Salicylates


Why is hemodialysis normally not used? what are some clinical indications of when it should be used? What are some characteristics of dialyzable toxins?

Most of time it is not necessary
Endogenous clearance adequate

 Consider use in patients who have renally-excreted toxin but inadequaterenal clearance
 Used in any setting for which it would
normally be indicated, poison or not
 Patient with potentially life-threatening
toxin load and severe symptoms unresponsive
 Patient is able to withstand significant
cardiovascular stress
 Toxin must be subject to removal by
this technique:

Molecular weight < 500 daltons
High water solubility
Low protein binding
less important in large dose poisoning
Low volume of distribution


How do we get lead in our bodies? Deficiency in what 3 elements increases lead absorption?

Paint in houses earlier than 1970, lead laden dust

 Pb absorption increased by co-existing deficiency of Fe, Ca, Zn


What ares some symptoms of lead poisoning? Are they early or chronic symptoms?

GI Symptoms:

 Early signs: vomiting, colicky abdominal pain, constipation
 More chronic: Gingival lead lines


 Chronic, children: developmental
impairment of IQ, hearing, growth, behavior
 Chronic, adults: peripheral motor neuropathy such as wrist drop

 Dense transverse metaphyseal bands (more dense than cortical bone) (chronic)
 Most prominent at knees, also in wrist, any other
long bone metaphysis, and in the axial skeleton


What is 3 antidotes for lead How does each work? When is each indicated? What are some adverse effects?

Calcium disodium Ethylene Diamine
Tetra Acetic acid (EDTA)
Chelates lead
 Can be used alone unless encephalopathy
or blood lead ≥70 mcg/dL:
 Combined dimercaprol (BAL) plus EDTA used together to prevent mobilization of lead into CNS
 Adverse effects: renal tubular toxicity &
removal of essential metals such as zinc & iron

Succimer, DMSA Dimercaptosuccinic acid
Water soluble, “heavy metal” chelator
 Treat childhood lead poisoning for blood
lead concentrations 45-69 mcg/dL
Also for arsenic, mercury & other metals
Better safety profile than the lipid soluble chelators such as CaNa2 EDTA, BAL, or water soluble penicillamine


What is arsenic? What does it react with? How do people get contaminated? What are some uses and sources?

 Arsenic is a metalloid
 Forms compounds with metals and C, N, O
 Either oxidized or reduced in chemical reactions

 Natural contamination of well water

 Local airborne contamination by burning high-
arsenic coal

 Dopant in silicon chip & semiconductor manufacture, as gallium arsenide or arsine gas
 Wood preservative “CCA’ (chromium, copper,
 No longer permitted by EPA for residential use
 Pesticides (insecticides, fungicides, herbicides)
 Homepathic & traditional-cultural medicines
 AsO3 salvage therapy for acute promyelocytic leukemia


What type of arsenic is most dangerous? What is the early course of arsenic poisoning manifest like?

 Trivalent arsenic is more toxic than
 Organic arsenic (shellfish) relatively non-toxic.

 Acute poisoning:
• Severe gastroenteritis including projectile vomiting, profuse "rice water" diarrhea, excruciating abdominal pain
Sudden drop in blood pressure, and encephalopathy


What is the antidote for early course arsenic poisoning? How does it work? What else is it used to treat? What should it not be used for? What are its adverse effects?

ANTIDOTE: BAL (British Anti-Lewisite):2,3 dimercaprol

 Di-thiol chelator binds arsenic into a stable complex & augments renal excretion
 For arsenic, mercury, gold
 For lead (only plus EDTA if…)
 Do not use for iron, cadmium or selenium

 Peanut oil suspension given IM (intra-
muscularly) and not IV (intravenously)
 Transient hypertension and tachycardia
 Fever
Pain at the injection site
 Nausea and vomiting
 CNS: headache, tremor, apprehension, fatigue, weakness
 Lacrimation and rhinorrhea


What does the later course of acute arsenic poisoning look like?

Damage to multiple organs
 Cardiomyopathy
 Rhabdomyolysis
 Renal failure
 Hepatic injury
 Bone marrow depression of all cell lines

Delayed sequelae (if patient survives)
Sensory-motor neuropathy
Skin eruptions, alopecia, and Mee’s lines


What happens with chronic arsenic poisoning?

 Weakness, malaise, anorexia, other GI
 Mild encephalopathy
 Tremors, ataxia, incoordination, confusion
 Peripheral neuropathy
 Painful paresthesias, muscle weakness & pain
 Hyperpigmentation, palmar- plantar hyperkeratosis, peripheral edema
 Skin cancer, also lung and bladder cancer


What are 3 different forms of mercury? Where are they found?

 Complex toxicology…various forms… different toxic profiles

 Elemental liquid mercury, Hg0
 Thermometers, control devices, dental

 Inorganic mercury, such as HgCl2
 Disinfectant, tannery, chemical synthesis

 Organic mercury, such as CH3Hg
 Fungicide manufacturing, embalming,
chemical synthesis


How does exposure to elemental mercury occur? How does acute exposure manifest? Chronic?

Inhalation hazard

Acute, high exposure … pneumonitis

Chronic exposure… renal impairment, gingivitis/ stomatitis/ ptyalism, “erethism”
• Neuropsychiatric abnormalities: personality changes such as shyness, withdrawal, excitability
• Insomnia, headache, memory loss, ataxia, altered taste & smell, anorexia, weight loss


What causes acrodynia? How does it manifest?

Due to Chronic mercury exposure

 Bright pink, painful, palmar-plantar, desquamating rash

 Classic presentation mercurial teething & diaper powders

 Painful peripheral neuropathy: diaphoresis, hypertension, fine tremors, weakness, irritability,
insomnia, anorexia

 High serum catecholamines

 Hypersensitivity reaction?


What happens with the ingestion of each three types of mercury?

 Acute ingestion of elemental mercury
 Non-toxic in most situations

 Acute ingestion of inorganic mercuric salts
 GIT corrosion, shock, acute renal failure

 Chronic ingestion organic mercury
 Severe central nervous system impairment


How is/was thallium used? How does thallium poisoning manifest?

 Former rodenticide; still has application as industrial chemical, homeopathic remedy, homicidal agent

1. Severe gastroenteritis
2. Delayed neuropathy (sensorimotor)
3. Alopecia in the second week – Complete baldness is characteristic


What is the antidote for thallium poisoning? What else is it used for? How does it work?

Prussian Blue

 Pigment …treats overexposure to thallium
and radioactive cesium (dirty bomb)

 Tl or Cs excreted into the bile, reabsorbed
in the gut and returned to the liver, which excretes them again in the bile……

 Oral Prussian Blue traps Tl or Cs in the gut, prevents re-absorption from the intestine and thereby increases fecal excretion
Reduces halflife


What are some examples of organophosphates?

Organophosphate compounds: Insecticides such as malathion & diazinon

Nerve agents sarin, soman, tabun, VX


What are the effects of organo phosphates? How do they work? How are they absorbed?

 Inhibit acetylcholinesterase

 “Age” on the enzyme, permanent deactivation

 Poisoning involves all cholinergic receptors

 Muscarinic: DUMBELS

 Nicotinic: excitation then fatigue of ganglia and
excitation then fatigue of skeletal muscle

 CNS: coma, seizures, central resp depression

 Easily absorbed through skin; risk of 2°

contamination to rescuers


What are two antidotes for organophosphate poisoning? How do they work? What do they do? How do you know if they're working? When should each be used?

 Treats muscarinic effects of cholinesterase inhibition (not nicotinic or CNS) as from OP & carbamate insecticides, “nerve agents, ” donepezil, muscarine-mushrooms, others
 Very high doses of atropine may be needed
 End point is dry respiratory secretions/ airway control

 Consider for severe poisoning only, not routine in all cases (atropine always!)
 Reverses organophosphate (OP) agent effects on the neuromuscular junction (fasciculations, weakness) by reactivating inhibited acetylcholinesterase
 Combines with OP-AChEsterase complex
De-phosphorylates the site before it AGES
Restores its ability to degrade acetylcholine