Download Toxidromes

University of Kentucky
College of Pharmacy
Pharmacotherapy – PPS 946
Frank Romanelli, Pharm.D., MPH, BCPS
Toxidromes
Cocaine
 Produces non-sustained feelings of euphoria.
 Sympathomimetic.
 Potentially lethal by all routes (snorting, IV, smoking, and PO).
 Poor oral absorption.
 Oral absorption can be toxic in cases of ruptured illegal body cavity transport.
 Smoked cocaine rapidly crosses the alveoli and the BBB.
 CVAs are a common manifestation of cocaine toxicity.
 Intracerebral and subarachnoid hemorrhages are also common.
 Seizures maybe induced.
 Cocaine induced chest pain is associated with MI.
 Rhabdomyalysis is common and maybe severe especially in patients presenting with
hyperthermia.
MANAGEMENT
Anxiety/psychosis
Sinus tachycardia
Hypertension
HA
Seizures
MI
Rhabdomyalysis
CVA
Diazepam/haloperidol
Observation/diazepam
Labetalol
CT Scan
Phenytoin/diazepam/CT Scan
Nitrates, CCBs, avoid beta-blockers
Alkalinization of urine (bicarbonate)
Supportive
Carbon Monoxide
 When inhaled binds to HgB to form carboxyhemoglobin.
 CO 250X the affinity for HgB when compared with oxygen.
 Present in all fires but of greatest concern in closed spaces.
 Diagnosis is made based on serum carboxyhemoglobin levels.
 Metabolic acidosis may be present as a result of inadequate tissue oxygenation.
 All patients with suspected CO poisoning should be placed on supplemental high
flow 100% oxygen.
 Patients with suspected carbon monoxide poisoning and depressed consciousness or
neurologic exam should receive aggressive therapy – consisting of hyperbaric
oxygen.
Tricyclic Antidepressants
 Involved in 12% of intentional drug ingestions and account for 36% of deaths.
 Always consider that cyclobenzaprine and CBZ are highly chemically and
structurally related to the TCAs.
 Cardiac toxicity:
Tachycardia and HTN from anticholinergic effects and reuptake inhibition.
Vasodilatation from peripheral alpha blockade.
Myocardial depression and cardiac conduction disturbances from inhibition of
fast NA+ channels.
CNS toxicity:
Sedation/coma from anticholinergic effects.
Seizures from NE and serotonin reuptake inhibition.
 Potent anticholinergic effects of these drugs may decrease emptying time and
increase toxicity.
 Symptoms progress rapidly.
 Clinical presentation: T(tonic-clonic seizures) C(cardiac) A(anticholinergic)
 Therapy is primarily supportive.
 Bicarbonate may reduce acute toxicity by two mechanisms:
1. Increased plasma protein binding of the TCA.
2. Stabilization of fast NA+ channels.
 Maintain serum pH 7.45-7.55.
 Do not induce emesis, consider lavage only if <1 hour from ingestion.
 QRS interval on EKG can predict impending toxicity:
QRS of 0.10-0.15 correlates with increased risk for seizures
QRS of 0.16 correlates with increased risk for both seizures and arrhythmias
QRS of < 0.10 does NOT however rule out the possibility of toxicity
 Physostigmine (an ACHesterase inhibitor) is contraindicated in TCA overdose due to
the potential for induction of seizures and asystole.
 If vasopressors are required norepinephrine and phenylephrine are recommended,
dopamine should be avoided secondary to depletion of amines.
Opioids
 Classic triad of opioid intoxication:
Miosis
Respiratory depression
Depressed level of consciousness
 Naloxone (2mg initially) is used to reverse respiratory depression.
 IV route is best but can be given down the ET tube.
 Considerably greater than 2mg of naloxone may be required to reverse the depressant
effects pentazocine, propoxyphene, codeine, and methadone (10-20mg).
 All opioids have a longer half-life than naloxone and repeated dosing or continuous
infusion of naloxone may be necessary.
 Continuous infusion is instituted at an initial hourly infusion dose of 2/3 the amount
in mg that was needed to reverse the respiratory depression.
Beta-blockers
Toxicity manifests as bradycardia and depression of inotropy.
Treatment is oriented toward reversing the negative inotropy.
In some cases atropine or pacing may be required.
Glucagon is the drug of choice for increasing inotropy. It does not compete with betareceptors.
Initially administer 3mg IV, may follow-up with continuous infusion.
Hydrocarbons
 Grade 2 hydrocarbons less toxic; toxicity mainly from aspiration and resulting
pneumonitis.
 With large ingestions of grade 2 hydrocarbons systemic absorption may occur
(cardiac toxicity, GI toxicity, CNS toxicity).
 Group 3 and 4 hydrocarbons are considered to be very toxic.
 GI elimination is indicated for all hydrocarbons when combined with another toxic
substance and for significant quantities of group 3 and 4.
Group 1 – greases – non-toxic
Group 2 – kerosene, gasoline
Group 3 – ring hydrocarbons – benzene
Group 4 – chlorinated hydrocarbons: carbon tetrachloride
Phencyclidine (PCP)
 Hallmark of PCP toxicity is violent or bizarre behavior.
 Patients may exhibit intermittent blank stare, intermittent facial grimacing,
intermittent abnormal posturing, irregular respiratory pattern, and visual
hallucinations.
 Self-induced injury is a primary concern.
 Treatment is supportive.
 Chemical calming may be achieved with haloperidol or diazepam.
Theophylline
 Toxicity is characterized by nausea, vomiting, and agitation – more serious
complications include dysrhythmias and seizures.
 Toxicity usually begins at serum levels greater than 20mg/l.
 Life-threatening toxicity is usually not seen with levels less than 50-60mg/l.
 Hypokalemia appears to exacerbate complications.
 Seizures are more likely to respond to diazepam than phenytoin.
 Patients should receive multiple dose activated charcoal and in cases of serum levels
greater than 60mg/l or severe seizures consider hemoperfusion.
Organophosphates/Pesticides
 Non-species specific, merely a question of dose.
 Nerve gases (US Soldiers carry Atropine and 2-PAM)
Organochlorines
 3 classes
1. dichlordiphenylethanes (DDT)
2. cyclodienes (heptachlor)
3. chlorinated benzene (lindane)
DDT – first synthesized in 1874, found to be very effective versus a variety of pests, use
has decreased secondary to environmental concerns, found to alter steriod metabolism
in birds resulting in death, banned in US and Europe but used heavily in
underdeveloped countries, absorption is primarily oral with only limited dermal
absorption.
Cyclodienes – among the most toxic and environmentally persistent toxins ever
produced. Very efficiently absorbed through the skin.
Lindane – commonly used for scabies and lice, absorbed through abraded skin and
mucous membranes, seizures common sign of toxicity.
Organophosphates
 Irreversibly inhibit the enzyme acetylcholinesterase. Carbamates are reversible
inhibitors.
 Carbamates toxic manifestations are the same as those for organophosphates but with
less severity and shorter duration.
 Some of these agents are known to have a characteristic “garlic-like” odor.
 Plasma cholinesterase levels can be assayed although this is rarely done.
 Potential deleterious effects on 3 body systems:
1. Parasympathetic – activation SLUDGE
2. Nicotinic – muscle weakness
3. CNS – confusion, slurred speech, respiratory depression
 Treatment:
1. Patients must remove all clothing and jewelry, decontamination of the skin with
copious flushing.
2. Atropine – used in moderate to severe poisonings, reverses muscarinic and CNS
effects, end-point is drying of secretions (dry mouth), dose: 2-4mg double every
5-10 minutes until effect. In massive exposures may need up to 100mg.
3. Pralidoxime (2-PAM) – cholinesterase re-activating agent, most striking effect is
at nicotinic sites, effects within 10-40 minutes, best if used within 24h of
exposure, does not penetrate the CNS. Dose: 1-2gm in 100-150cc NS over 30
minutes, may repeat every 6-12h for 24-48h. Administer slowly some patients
have developed respiratory arrest following rapid infusions.
Anecdote: Epidemic poisoning occurred during prohibition when a brand of alcoholic
Jamaican Ginger Extract was adulterated with tri-o-tolyl-phosphate (TOTP).
Barbituates
 Act to potentiate GABA mediated neuro-transmission.
 Characterized by respiratory depression, hypotension, and decreased level of
consciousness. Hypotension a result of reduced sympathetic tone and contractility.
 Toxic dose is generally 5-10X the hypnotic dose.
 Clinical presentation: slurred speech, lethargy, ataxia, hypothermia, coma, death.
Patients may appear “dead.”
 Diagnosis based on clinical presentation and tox screen. PB levels (15-40mg/l
therapeutic).
 Standard therapy consists of support and GI elimination.
 Forced diuresis, alkalinization of the urine (only with PB), and multiple dose charcoal
will all enhance elimination.
 Ultrashort acting (duration <30 min)
Lipid soluble and rapid penetration of the brain
Methohexital
Thiopental
 Short-acting
Pentobarbital
Secobarbital
 Intermediate-acting
Amobarbital
Aprobarbital
Butabarbital
 Long-acting (duration >6-12h)
Mephobarbital
Phenobarbital (t1/2 80-120h)
Benzodiazepines
 Death from benzos is rare – UNLESS combined with alcohol or other CNS
depressants.
 Clonazepam (Klonopin®) $3.00 street price.
 Act to enhance GABA-minergic neurotransmission.
 High toxic-therapeutic ratio.
 Clinical presentation: lethargy, slurred speech, ataxia, respiratory depression, coma.
 Diagnosis: tox screen and clinical presentation.
 Avoid emesis especially with ultra-short acting products (midazolam, triazolam,
temazepam) due to rapid progression to coma. Use activated charcoal.
 Flumazenil (Romazicon®) indicated for pure benzo overdoses only. Contraindicated
in cases of TCA overdose and in patients with history of seizure disorder.
 Dose: 0.2mg IV repeat with 0.5mg q1min until response achieved or to a max dose of
3mg.
Alcohols
Methanol
 Common components of gasoline, antifreeze, windshield washer fluid, photocopying
fluid, wood alcohol, paint thinner, household cleaners, shellac, and varnishes.
Colorless liquid.
 When ingested it is rapidly absorbed from the GI tract, it may also be absorbed from
cutaneous absorption or “huffers”.
 Methanol is mildly inebriating and does not result in toxicity itself but from its
metabolites. MetOH is slowly metabolized to formaldehyde in the liver by alcohol
dehydrogenase and subsequently to formic acid by aldehyde dehydrogenase.
 Formic acid accumulates within the optic nerve and may result in blindness, it also
may lead to metabolic acidosis.
 Formic acid is converted to CO2 and H20 via a folate dependent mechanism.
 In toxic ingestions an osmolar gap will be seen an anion gap usually but not always
develops.
 Following a 72h latent period after ingestion patients develop visual disturbances
(“like standing in a snowfield”), CNS disturbances and slurred speech.
 The latent period will be prolonged in concurrent methanol/ethanol ingestions.
 Diagnosis based on presentation and calculation of osmolar/anion gap.
 Always draw concurrent ASA/APAP and ethylene glycol levels.
Treatment consists of supportive care, avoid ipecac, charcoal is ineffective.
Ethanol therapy: EtOH will competitively and preferentially bind alcohol
dehydroygenase and prevent further MetOH metabolism. Load with 10% EtOH in
D5W over 30-60 minutes then start 1.39ml/kg/h of a 10% EtOH solution.
Folinic acid (Leukovorin®) and folic acid will enhance the conversion of formate to CO2
and H2O.
4-methylpyrazole/Fomepizole (4-MP) (Antizol®) has the advantage of blocking the
effects of alcohol dehydrogenase without causing inebriation. EXPENSIVE.
Hemodialysis rapidly removes methanol and formate from the circulation. It is indicated
in more severe cases of ingestion and can be used concurrently with EtOH or 4-MP.
Ethylene Glycol
 Primary ingredient (95%) of antifreeze. Also found in coolants, de-icers, paints,
brake and hydraulic fluids. Formerly used as a vehicle for some pharmaceuticals and
European wines.
 EG is a colorless, odorless, sweet-tasting, water-soluble liquid.
 EG has a very high boiling point (198dC) and a very low freezing point (-13dC).
 Lethal dose is 1.5ml/kg or 100ml for a 70kg person. There is a documented report of
survival following a 2 liter ingestion.
 EG is usually ingested but can be absorbed through the skin or inhaled.
 EG has some inebriating properties and is a gastric irritant.
 Approximately 20-50% is excreted in the urine while the remainder is metabolized in
the liver.
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EG is metabolized to glycoaldehyde by alcohol dehydrogenase, glycoaldehyde is
metabolized by aldehyde dehydroygenase to glycolic acid. The accumulation of
glycolic acid causes renal tubular damage. Glycolic acid is further metabolized to
glycoxylic acid then oxalic acid. These acids contribute to acidosis. Oxalic acid is
rapidly converted to calcium oxalate crystals (crystals develop within 1-3h of
ingestion) which accumulate in various tissues.
Glyoxylic acid is eventually converted to CO2 and H2O by a folate and pyroxidine
dependant pathway. This pathway also requires magnesium and thiamine.
Clinical presentation:
Stage 1 - The CNS Stage: lasts 30min to 12h, characterized by intoxication, slurred
speech, lethargy, ataxia. Patients may complain of GI distress.
Stage 2 - The Cardiac Stage: occurs 12-48h after ingestion and is characterized by
cardiac edema, cardiac dilation, and the development of arrhythmias. Death is most
common during this stage.
Stage 3 – The Renal Stage: occurs 24-72h following ingestion and is characterized
by the development of acute renal failure, pts. complain of flank pain and have CVA
tenderness on PE.
Diagnosis based on presentation/presence of calcium oxalate crystals. Many
antifreeze products contain sodium fluorescein – so the vomitus, NGT aspirate, or
urine may fluoresce under a Woods Lamp.
Draw EG levels as well as ASA/APAP, place pts. on EKG monitor.
Treatment
If Ingestion has occurred within 4 hours then gastric lavage should be performed.
Treat symptoms (e.g., arrhythmias) supportively.
Correct metabolic acidosis with bicarb.
Treat hypocalcemia with calcium chloride or calcium gluconate.
Ethanol: use same dosing as with MetOH ingestion and for the same pharmacologic
mechanism. Begin ethanol therapy immediately in suspected ingestions. DO not
delay.
4-MP is an alternative to ethanol therapy.
Thiamine, pyridoxine, and folate should all be administered to enhance rapid
conversion glyoxylic acid to it non-toxic metabolites.
Hemodialysis should be employed in severe cases involving ARF or high serum EG
levels (>50mg/dl).
Isopropyl Alcohol
 Widely used as a solvent, antiseptic, and disinfectant. Commercially available as
“Rubbing Alcohol” (70% solution). Found in skin lotions, aftershave, dog repellents,
de-icers, and window cleaning fluids.
 Often ingested by alcoholics as a cheap substitute for ethanol.
 Bitter taste and distinctive odor.
 Lethal dose is dependent upon individual tolerance.
 Clinically significant absorption can occur by inhalation and dermal application, esp.
a concern in pediatrics.
 Metabolized by alcohol dehydrogenase to acetone, which leaves a sweet fruity odor
on the breath. Acetone is eliminated by the kidneys and lungs.
 IA is 2-3X more potent as a CNS depressants when compared to EtOH and has a
greater capacity to cause GI irritation/gastritis. Large dose of IA will cause
hypotension secondary to myocardial depression and vasodilation.
 Clinical presentation is similar to EtOH with the exception of more GI irritation and
the persistence of CNS depression for a longer period of time.
 Diagnosis is based on symptoms/presentation, the presence of ketosis (sweet odor on
the breath). Clinical pearl – will see an osmolar gap without and a non-anion gap
metabolic acidosis.
 Treatment is primarily supportive, do not induce emesis, gastric lavage is indicated
only if within 2 hours of ingestion, activated charcoal of no benefit.
 In cases of severe toxicity HD should be considered. (hypotension should be the
guiding parameter in decisions to use HD).
Ethanol
 Chemical beer and ale are 2-8% EtOH, wines 10-20% EtOH, and liquors contain 2095% EtOH. EtOH is also found in colognes, perfumes, aftershave, mouthwashes,
antiseptics, and pharmaceutical preparations (e.g., elixirs, Nyquil®).
 In the US - % alcohol by volume multiplied by 2 is referred to as “proof” of the
distilled spirit.
 Clear, colorless fluid.
 In a 70kg person with an empty stomach, the ethanol in 3-4 drinks of whiskey would
result in a BAL of 100mg/dl within 30min-3h and would take 5-6h to be completely
metabolized.
 Lethal dose varies but is in the range of 5-8gm/kg.
 Rapidly absorbed from the GU tract with blood levels within 5 min of ingestion.
 Metabolized by alcohol dehydrogenase to acetaldehyde which is then metabolized by
aldehyde dehydrogenase to acetyl CoA. Acetyl CoA is eventually metabolized to
CO2 and H2O.
 Ethanol acts in the CNS to disrupt ion transport, preventing the generation of
neuronal impulses. Neurons of the RAS are the first to be affected.
 Clinical presentation: paradoxical CNS stimulation followed by disinhibition.
Severe intoxication can result in respiratory depression and coma. Hypoglycemia
may result from the inhibition of gluconeogenesis. Ethanol impairs thermal
autoregulation and increases cutaneous bloodflow – predisposing to hypothermia.
Ethanol Level (mg/dl)
30
50
100
200
300
400+
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Clinical Manifestation
Mild euphoria and disinhibition
Mild incoordination
Ataxia
Drowsiness and confusion
Stupor
Respiratory failure, coma, death
There is marked variations in alcohol tolerance death has been reported after a level
of 260mg/dl and complete recovery after a level of 1510mg/dl (female).
Diagnosis – usually simple and based on presentation. Be cautious of co-ingestions
… a level of <300mg/dl in a comatose patients warrants a search for other potential
causes.
Both an osmolal and anion gap can be expected.
Treatment is mainly supportive, protect airway to prevent aspiration. Administer
thiamine, glucose, and naloxone.
Gastric lavage can be considered if with 30min of ingestion. Charcoal is of no use.
Administer IV fluids to patients since dehydration will accompany ingestion.
Administer “banana bag” to all chronic alcoholics (D5NS with 100mg thiamine, 1mg
folate, 1 amp MVI, and 2gm MgSO4).
HD effectively removes ethanol but is rarely needed.
Acetaminophen
 APAP is a metabolite of phenacitin (removed from market due to renal failure and
metHB).
 APAP is rapidly absorbed from the GI tract.
 Mainly hepatically metabolized with only 2-5% of the drug being renally excreted
unchanged.
 Liver responsible for the conjugation (90%) to glucuronide and sulfate metabolites.
 <5% of APAP will be metabolized by the CP-450 system to N-acetyl-p-benzoquinoneimine. This is a toxic intermediate metabolite which is inactivated by
conjugation with glutathione.
 Patients who ingest large doses of APAP will overwhelm the normal conjugation
pathway and shunting occurs to CP-450 pathway. This results in accumulation of the
toxic metabolite as glutathione stores rapidly become depleted. The toxic metabolite
is directly hepatoxic.
 Manifestation of toxicity usually follows a latent period (12h-3days).
 Classically, there are 4 phases of APAP toxicity:
PHASE 1
First 24h, GI upset, N/V, sweating.
PHASE 2
24-27h, clinically pt, feels better and may be entirely asymptomatic, hepatoxicity
develops and LFTs rise and peak usually around 72h.
PHASE 3
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>72h, hepatic dysfunction continues, pts. begin to clinically deteriorate, PT/INR
elevates, increased ammonia levels, may result in hepatic encephalopathy/death.
PHASE 4
5-14d, resolution of hepatic impairment.
Acetaminophen levels are obtained 4 hours following ingestion and are then plotted
on the Rumack-Matthew Nomogram. This nomogram is used to guide clinical
decision making on the treatment of APAP toxic ingestion. Nomogram is difficult to
interpret in cases of ingestion with extended release products.
Antidote is N-acetylcysteine (NAC or Mucomyst®). NAC is effective up to 12h
post-ingestion and is still utilized with some hope up to 24 post-ingestion.
Begin NAC therapy if:
>4h and pt. Is in potentially toxic range
APAP assay will be delayed and a significant ingestion is suspected
NAC acts to replenish glutathione stores with the liver. It is composed of many –SH
groups and those has an extremely noxious odor and taste.
Dosing: load with 140mg/kg and follow with 70mg/kg q4h X 17 doses.
Mix NAC in fruit juice to mask taste/odor.
For vomited doses repeat dosing. Patient should receive 17 complete doses.
Methods to improve likelihood of keeping drug down: metoclopramide IV, IV
droperidol, IV ondansetron, NGT infusion.
Lavage is perferred over ipecac as the patient may be more tolerant of NAC.
Charcoal also may bind NAC and its use with NAC is considered to be controversial
at this time.
Acetadote®: 150 mg/kg Load followed by 50 mg/kg over 4h, then 100 mg/kg over
16h. Administered in D5W. High D load. Monitor - hyponatremia.
Cimetidine – experimental therapy.
Aspirin/Salicylates
 Acetyl-salicylic acid (ASA)
 Methyl-salicylate (Oil of Wintergreen) (1ml=1.4gm ASA) MOST TOXIC
SALICYLATE
Pathophysiology of Salicylate Ingestion
PRIMARY EFFECTS
SECONDARY EFFECTS
Direct CNS and resp. center stimulation
Respiratory alkalosis
Uncoupling of oxidative phosphorylation
Metabolic acidosis
Inhibition of krebs cycle enzymes
Impaired glucose metabolism
Inhibition of amino acid metabolism
Water and electrolyte loss
Interference with hemostatic mechanisms
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Due to the acidic nature of salicylates they have a self-promoting absorption
phenomenon in toxic ingestions.
presentation:
CNS
Initial stimulation of the resp. centers of the brain with resulting hyperventilation and
resp. alkalosis
Tinnitus and ototoxicity
Late depression of CNS with resultant hypoventilation
Skeletal Muscle
Uncoupling of intracellular oxidative metabolism which results in “run-away”
cellular metabolism and metabolic acidosis, increased production of heat and
depletion of glucose.
Acid/Base Renal
Increased re-absorption of salicylates from the renal tubules secondary to acidosis.
Lungs
Pulmonary edema due to capillary leak.
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Degrees of toxicity from acute ingestion:
<150mg/kg unlikely toxicity
150-300mg/kg mild-moderate
>300mg/kg potentially severe
>500mg/kg potentially lethal
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Diagnosis:
Clinical Features
Nausea
Vomiting
Tinnitus
Hyprenea
Hyperpyrexia
Disorientation
Coma
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Lab Abnormalities
Hypo- or hyperglycemia
Hypo- or hypernatremia
Hypokalemia
Resp. alkalosis (initially)
Met. acidosis (latent)
Abnormal LFTs
Renal impairment
Done Nomogram is used to make clinical decisions on the treatment of ingestions.
Blood levels are drawn at 6 hours post-ingestion.
Nomogram cannot be used in cases of chronic ingestion, ingestion of enteric or SR
preparations, ingestion of oil of wintergreen (rapid absorption), uncertain or unknown
time of ingestion.
Nomogram is limited and its use is controversial some clinicians treat based on serial
ASA levels.
Treatment: centers around alkalinization of the urine to enhance ionization and
promote excretion.
Alkalinization of the urine also reduces penetration into the CNS.
Indicated when serum salicylate level is >30-35mg/dl.
Method: Blous with 1-2mEq/kg of bicarb and follow with 100-150mEq bicarb in
D5W 1l @ 150-200cc/hr.
Add K+ to bag, goal is for urine pH of 7.5-8.0.
HD may be indicated in cases of serious ingestions with salicyclate levels >100mg/dl.
Cyanide
 Found in photography equipment, fumigations, electroplating, produced by the
burning of PVC and organic materials in fires (found in 50% of fires – clinically
significant in 10%), is a metabolite of acetonitrile (nail-polish remover), cyanogenic
pitted plants (e.g., peaches), iatrogenic (metabolite of sodium nitroprusside).
 Non-specific inhibitor of the cytochrome oxidase system. This system functions in
the electron transport chain located in the mitochondria. Its function is to convert
glucose to ATP. Cyanide inhibits this process, thus the organism is forced to convert
to anaerobic metabolism. The two major consequences of the conversion to
anaerobic metabolism are: formation and accumulation of lactic acid (over prolonged
period of time) and decreased oxygen metabolism.
 Symptoms reflect the dysfunction of oxygen sensitive tissues:
CNS – anxiety, lethargy, coma, agitation
CV – bradycardia and hypotension
GI – abdominal pain and emesis
Skin – early cherry red (best appreciated in the fundi); late cyanotic
Cyanide classically associated with smell of “bitter almonds”
Diagnosis based on presentation, cyanide levels not clinically useful due to long turnaround time.
When to suspect cyanide poisoning:
Sudden collapse of lab or industry worker
Fire victim with coma and acidosis
Suicide with acidosis and unexplained coma
Ingestion of nail polish remover
ICU patient on sodium nitroprusside (Nipride®) with MS changes or unexplained
acidemia
 Antidote: LILLY CYANIDE ANTIDOTE KIT
1. Amyl Nitrite pearls: to be used while IV access is being secured
produces 3% metHB
2. Sodium Nitrite:
produces 20-30% metHB in 30min
supplied as a 3% solution
10ml over 4min as BP tolerates
Check metHB level in 30min
3. Sodium Thiosulfate: acts as a sulfur donor to the endogenous enzyme rhodanse
directly complexes to cyanide to form thiocyanate
supplied as a 25% solution
50cc IVP
Amphetmaines
 Toxicity is similar to cocaine.
 Patients present with HTN, seizures, tachycardia.
 Treatment is supportive.
Digoxin
 Derived from foxglove plant.
 Primarily excreted renally.
 Toxic dose >0.05mg/kg or level greater than 2.0ng/ml.
 Toxicity comes from inhibition of the NA-K-ATPase pump. Resulting in loss of
intracellular potassium and gain of intracellular sodium and calcium.
 Clinical presentation:
G/I – nausea/vomiting
CNS – mental status changes
CV – sinus and AV block, bradycardia
Eyes – visual disturbances, yellow/green haze and halo vision
Diagnosis based on history, EKG, serum potassium levels.
Treatment:
Hyperkalemia – bicarb, glucose, insulin, sodium polystyrene (Kayexalate®)
Bradycardia – atropine, pacemaker
 Digibind® (digoxin Immune Fab)
Sheep derived digoxin specific IgG antibodies
Antibodies bind active drug rendering it inactive
Total digoxin levels will rise but free digoxin levels will fall
Elevation in levels is a false elevation, since drug will not be active – do not draw
levels for 72h since they will not provide any true clinical information
Indicated only for life-threatening hyperkalemia or life-threatening arrhythmias
Each vial of digibind® will bind 0.6mg of digoxin
Give sufficient amount of digibind to counteract ingested dose
Keep in mind that therapeutic effects of digoxin will also be reversed
Expensive
 HD is ineffective.
Calcium Channel Blockers
 Toxic effects … coronary and peripheral vasodilation, decreased cardiac contractility,
decreased sinus node activity, decreased AV node conduction, selectivity in site of
action (vasculature versus myocardium).
 Clinical presentation will involve bradycardia and vasodilation. Non-cardiac
symptoms may include: nausea, vomiting, stupor, confusion.
 Treatment: supportive (ABCs), monitor vital signs and EKG for at least 6h.
 Specific drugs:
Calcium – reverses depression of cardiac contractility, no sinus node effects or effects
on peripheral vasodilation.
Glucagon – stimulates formation of adenyl cyclase, adenyl cyclase increases
intracellular cAMP. End result is positive inotrope and chronotrope. Dose: 5mg IV,
then 3mg/h.
4-amniopyridine – experimental, commonly used outside of the US.
 HD usually not effective due to high plasma protein binding.
Iron
 Used as a daily vitamin supplement, common scenario is a pregnant mom with a 2year old at home.
 Formulations:
Child: 15-18mg (Fe)/5cc
Adult: 60-90mg (Fe)/dose
 Toxicity from direct corrosive effects on the mucosa and excessive iron may lead to
cellular dysfunction accompanied by acidosis (exact mechanism unknown).
 Toxic doses:
Symptoms unlikely: <20-30mg (Fe)/kg
Potentially serious: >40mg (Fe)/kg
Potentially lethal: >60mg (Fe)/kg
Acute lethal (animal studies): 150-200mg (Fe)/kg
Lowest reported lethal (child): 600mg
Clinical Presentation – 4 Classic Stages
Immediate – corrosive effects, emesis, bloody diarrhea
Latency – period of improvement usually over 12h
Relapse – abrupt onset of coma, shock, seizures, coagulopathy, hepatic failure, and
death
Late – scarring from corrosive injury, strictures, obstructions
 Diagnosis – based on history, AXR may show radio-opaque pills
 Levels:
Toxicity likely if serum Fe>450mcg/dl
Serum Fe > TIBC
 Treatment: ABCs
 Deferoxamine
Used if serum Fe >500mcg/dl
Start at 10-15mg/kg/h
Follow – orange to pink (vin rose) urine
Color is a result of the chelation of iron by deferoxamine
Stop when serum Fe is normal or urine color is normal
 Lavage may be helpful when AXR shows persistence of tablets.
 Do not lavage with deferoxamine – this promotes Fe absorption
 HD and charcoal useless.
Vitamins
 Water versus fat soluble.
 Toxicity usually a result of chronic overuse.
 Vitamin A – increased intercranial pressure.
 Vitamin D – increased calcium absorption with resultant hypercalcemia.
 Niacin – histamine release, flushing, pruritus.
 Pyridoxine (B6) – altered neuronal conduction, ataxia, poor muscle coordination.
Holly and Mistletoe
Not lethally toxic to humans.
Gastroenteritis.
Silca Gel
 Sand – non-toxic.
Spiders
 50,000 species in the US, 3 cause significant envenomenation.
Black Widow
 Shiny black with a red hourglass shape on the abdomen.
 Bite often initially unnoticed.
 Venom is a neurotoxin which leads to increased inflow of calcium and release of
Ach. Thus, symptoms are painful fasiculations and cramping. The quicker the
symptoms occur after the bite – the more severe the reaction will be.
 Treatment: general wound care and cleansing, tetanus shot if indicated.
 IV calcium gluconate for cramping.
 Anti-venin: used for patients not responding to conventional therapy. 1-2 vials
usually requires – horse derived with risk of anaphylaxis.
Brown Recluse
 Light brown with a violin shaped marking on its back, very shy.
 Bite: painful, burning sensation within 10 minutes. Venom is a potent vasoconstrictor
similar to NE. Over next 12h, a bulls-eye lesion forms. Over next 1-3 days area
becomes necrotic and may last for months.
 Systemic symptoms usually occur by day 1-2 and include fever, chills, malaise, and
in worst case scenario DIC.
 Treatment: general wound care, tetanus if indicated, dapsone within the first 24h may
reduce lesion size. Excision not recommended. No anti-venin.
Jumping Spider
 Painful bite with local blister-like reaction.
 Systemic symptoms are similar to that seen with Brown Recluse but less likely to
develop DIC.
 Treat in same manner as Brown Recluse bite.
Snakes
Pit Vipers (Crotalidae)
 Includes: diamondbacks, rattlesnakes, copperheads, cottonmouths.
 Triangular shaped heads, facial heat-sensing pit between eyes and nostril, moveable
hinged fangs, single row of scales.
 Venom: complex mixture of factors which contains neurotoxic and coagulopathic
compounds. Varies from snake to snake and by time of year.
 Manifestations: immediate pain which is confined to the bite area, edema,
ecchymosis, and petechiae.
 Up to 20% of bites are dry.
 Seriousness of envenomation: rattlesnake>cottonmouth>copperhead
Elapidae
 Includes: coral snakes, cobras, kraits, mambas.
 Shy, non-aggressive snakes; small, narrow, round heads; fixed fangs; no pits.
 Manifestations: generally minimal swelling and inflammation.
 Systemic: maybe delayed up to 12h, symptoms tend to be more neurotoxic: MS
changes, double vision, slurred speech, generalized weakness.



Overall Treatment:
Keep pt. calm
Transport to HCF ASAP
Remove any constricting clothing or jewelry around site of bite
Immobilize bitten extremity below level of the heart
Tetanus if indicated
Broad spectrum antibiotics
Antivenins:
Extent of the bite and reaction will determine whether or not to use antivenin and the
appropriate number of vials to be used.
Crotalidae: Polyvalent is effective for all pit vipers found in the western hemisphere
as well as some South American Pit Vipers and some Asian snakes. It consists of
horse serum IgG which means high risk of anaphylaxis … esp. if pt. has received
antivenin previously. Should be given ASAP in order to have full effect.
Coral Snake: Monovalent and only useful for E coral snake venom.
Exotic snakes: Antivenin may be available via AZ PCC (602-626-6016) or the
American Association of Zoological Parks and Aquariums (304-242-2160)
University of Kentucky
College of Pharmacy
Pharmacotherapy PPS 946
Frank Romanelli, Pharm.D., MPH, BCPS
Clinical Toxicology
GOAL
To review the clinical approach to the management of patient presenting with
common clinical toxidromes.
Objectives:
Upon completion of this toxicology module the learner should be able to:

List the most common clinical presentation for each toxidrome presented.

Differentiate between various toxidromes.

Formulate care plans and predict outcomes for common clinical toxic ingestions.