topic 24 Flashcards
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
reservoir
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
In CNS:
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,
arsenic)
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
pentavalent
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
amalgam
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
- Severe gastroenteritis
- Delayed neuropathy (sensorimotor)
- 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?
Atropine:
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
Pralodoxime:
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
