Toxicology Flashcards
(31 cards)
What do Anticholinergics do?
The competitively inhibit Ach (acetylcholine) accessing muscarinic receptors in the CNS, and cholinergic nerves in smooth muscle, secretory glands and eyes.
Includes TCA’s, antihistamines, atropine and scopalamine.
Many involve sodium channel toxicity, GABAa and K+ block.
Most common OD is Benadryl
Common ECG changes in anticholinergic poisoning
Includes TCA’s
- Sinus tachycardia
- wide QRS (>100 prep for seizures, >160 prep for vfib/vtach)
- Long QT
- Tall R in aVR
- RAD
Anticholinergic poisoning s/s
- similar to sympathomimetic (tachycardia, hypertensive), but skin is dry, there are fewer bowel sounds and no change to respiratory rate.
Treatments for anticholinergic poisoning
- Symptom management: avoid beta blockers in rhythm management*
- sodium bicarbonate
- physostygmine (increases circulating Ach)
Call poison control!
Because beta blockers act directly on the sympathetic nervous system (which is already in overdrive), they can cause an excessive drop in HR and blood pressure leading to incrased incidence of cardiac arrest. If needed, consider CCB’s.
What factors increase risk of SSRI toxicity?
- Extremely large doses (150x)
- Taken with ETOH, benzo’s or TCA’s
What do SSRI’s do, and what are signs and symptoms of SSRI toxicity?
They inhibit the reuptake of seratonin and norepinepherine
s/s include: tachycardia, seizures, agitation, flushing, diaphoresis and long QTc
Treatments for SSRI toxicity
- ECG monitoring (QRS>100ms prepare for seizure activity, >160 prep for vtach/vfib)
- Sodium bicarb to increase Na+ gradient and narrow the QRS. Consider hypertonic saline as an alternative if reaching pH 7.55
- benzos/propofol for seizures. NO phenytoin due to further Na+ blocking effect
Treatment is largely supportive
What causes cholinergic toxicity?
Organophosphates cause cholinesterase inhibition, with primarily muscarinic effects.
Carbamate insecticides and non-regulated fertilizers are common culprits.
s/s of cholinergic toxicity
Salivation
Lacrimation
Urination
Defication
Gastric
Emesis
Bronchorrhea
Bronchospasm
Bradycardia
Also causes mydriasis (pinpoint pupils)
Treatment for cholinergic poisoning
- atropine - to effect, to dry secretions
- 2PAM (pralidoxime), with atropine, must be administered early before the organophosphate molecule ages. (reactivates cholinesterase by replacing bind with organophosphate)
- epinepherine as pressor
- NO succinocholine due to prolonged duration (cholinesterase degrades it, and cholinergics prevent cholinesterase)
Treatment is largely supportive; not all facilities will have 2PAM
Action of Sympathomimetics
Block reuptake of seratonin, nor-epi and dopamine. Sodium channel blockade.
Common culprits are cocaine, MDMA, amphetamines, caffeine
s/s of sympathomimetic toxicity
*tachycardia
* chest pain
* arrythmia
* Na+ channel blockade
* hypertension
* agitation
* dilated pupils
* perspiration/chills
Very similar to anticholinergic toxicity but skin is damp, and resp rate and bowel sounds increase.
Treatment for sympathomimetic toxicity
- Benzodiazepines are first line
- ASA & nitro, nitroprusside can also be considered
- NO succinocholine due to increased acidosis
- NO beta blockers due to unopposed adrenergic effects; consider CCB’s if needed
- NO tylenol for hyperthermia: problem is not in the hypothalamus
Care is largely supportive
Mechanisim of Acetaminophen toxicity
When pathways for metabolizing acetaminophen are overwhelmed, NAPQI is produced faster than the glutathione that neutralizes it, and hepatotoxicity follows after the first 4 hours.
4 pathways of acetaminophen metabolism
- Glucarondination (40-67%)
- Sulfation (20-46%)
- CYP450 (5-15%) This pathway produces the hepatotoxic compound NAPQI, which is neutralized by glutathione stores…to a point
- Unchanged (5%)
All are excreted in urine
Lab indications of acetaminophen toxicity
- APAP values over 10 mcg/mL
- marked AST/ALT increases >3000 IU/L = acetaminophen induced hepatitis
- increased PTT/INR
Rumack Matthew line is used to determine whether timeline and serum levels indicate NAC administration.
Treatment for acetaminophen toxicity
- Activated charcoal to absorb undigested toxins may be considered in first hour.
- NAC (N-acetylcysteine) is given after four hour mark* to enhance non-toxic pathways: increases sulfation, glutathione production and is a free radical scavenger and antioxidant. Administer until APAP serum concentration is < 10 mcg/mL and liver enzymes normalize.
- ECMO may be considered if patient is decompensating into multi organ failure.
*usually based on Rumak Matthew line, but give if unsure of timeline/hx
What constitutes a lethal dose of acetaminophen?
In general, lethal doses are > 150 mg/kg in acute setting, or over 10g daily for chronic ingestion.
What do salicylates do, and what are toxic levels?
Weak acids that interfere with aerobic metabolism by inhibiting the electon transport chain in the mitochondria. As a result, cells switch to anaerobic metabolism causing lactic acidosis.
- 200-300 mg/kg is toxic
- > 500 mg/kg is lethal
s/s or salicylate toxicity
- Respiratory alkalosis due to deep hyperventilation
- HAGMA due to aerobic metabolism interruption
- Hyperthermia from increase in anaerobic pathways (no Tylenol needed)
- Pulmonary and cerebral edema as respiratory compensation fails and switches to respiratory acidosis
- Hypokalemia - often there is excessive vomiting due to activation of the chemoreceptor trigger zone (CTZ) from hyperventilation
- Hypoglycemia from glucose metabolism interruption and increased metabolic demand (depletes glycogen)
- ALOC
- Tinnitus
Treatment for salicylate toxicity
- Correct fluid status, but do NOT overload
- Correct hypoglycemia remember if serum BGl is low, it’s even more dire in the brain due to increased demand
- Correct HypoK+ which will trap H+ ions in the urine for excretion. It works on the H-K+ pump in the kidneys to equalize.
- Alkanize urine by administering 3 amps of sodium bicarbonate in one litre of D5W (NOT n/s due to increased Na+ that would occure) and run at 150 mL/hr. Target pH of 7.4 to 7.8.
- Dialysis is indicated in increased serum levels over 100 mg/dL, ALOC, repiratory depression, edema, severe acidosis and deterioration despite above treatments.
TCA receptor effects
Na+ block: arrythmias weakness, seizures, ALOC
a1 adrenoreceptor block: vasodilation, smoot muscle relaxation, hypotension
Norepi & seratonin block: tachycardia, hypotension, confusion, seizures, coma
Muscarinic block: pupil dilation, bronchodilation, tachycardia, decreased secretions and GI motility
Histamine block: sedation, seizures, hypo/hypertension, arrythmias, tachycardia, fever
K+ efflux blockade: QT prolongation, Torsades de Pointes, agitation, confusion
GABAa antagonism: decreased inhibitory neurotransmission and increaced neuroexcitation = seizures, agitation
How do beta blockers work on the three different Beta receptors?
B1 (selective and non-selective)
* reduce myocardial contraction (inotropy),
* decrease cardiac conduction (dromotropy) and
* decrease heart rate (chronotropy)
Selective BB’s propanolol and acebutolol inhibit fast Na+ channels and can widen the QRS; because propanolol is also lipophilic it can cross the BBB and cause ALOC. Sotalol blocks slow K+ channels, prolonging the QTc
B2 (non selective)
* reduce smooth muscle relaxation in blood vessels
* reduce glycogenolysis and glucogenesis in liver leading to hypoglycemia
* decrease bronchodilation in lungs
* decrease smooth muscle relaxation in uterus
B3 (non selective)
* decreased release of free fatty acids from adopose tissue
Overall they block norepi and epi from working on the beta receptors.
Treatment of BB & CCB toxicity
Atropine is largely ineffective, but worth a shot as an emperical treatment. May work against bowel irrigation.
Ca++ to increase intracellular Ca++ and contractility. 1-3g push q. 3-5 min
Glucagon in BB can increase cAMP for increased contractility independent of B1 pathway. 3-5mg slow push, repeat once in 5 min - will cause nausea
Insulin/D10 to optimise glucose metabolism to support cardiac cells. Monitor K+ abd keep 2.8-3.2 mEq/L. Insulin 1U/kg bolus followed by 1U/kg/hr infusion. D10 25-50g bolus prior to insulin, then 0.5g/kg/hr titrated to euglycemia
Catecholamines norepi is “go to” with goal of MAP 65 or mentation
Lipid emulsion in desperation when pt is peri-arrest.
Other sodium bicarb in BB agents causing Na+ blockade, pacing, dialysis, ECMO.
Similar presentations and treatment with the exception of decreased BGl in BB’s and increased BGl with CCB’s
