Toxicology Flashcards
Acid-base disturbances with aspirin toxicity?
Early respiratory alkalosis followed by anion gap metabolic acidosis [MIXED respiratory alkalosis and metabolic acidosis – pH will be normal in a pt with mixed disturbances, low pCO2, low bicarb]
Respiratory alkalosis due to stimulation of respiratory center from aspirin which crosses BBB leading to hyperventilation – loss of CO2 leading to low paCO2.
Metabolic acidosis then occurs as there is increased production of endogenous acids (lactic acid and ketone bodies) rather than the salicylate itself.
What are the cases of metabolic acidosis with aspirin toxicity?
- inhibition of dehydrogenases in Kreb cycle – causing accumulation of acetyl-CoA preventing production of more acetyl coA leading to lactate formation – leading to pyruvate and lactic acid accumulation
- uncouple of oxidative phosphorylation - leading to production of ketone bodies due to elevated acetyl CoA
- salicylates impair renal function leading to sulfuric and phosphoric acid
- increased renal excretion of bicarb as a compensatory response for respiratory alkalosis
- salicylates ARE weak a acids
Clinical presentation of aspirin toxicity?
- vomiting post ingestion leading to HYPERPNEA (increased depth and rate of breathing), TINNITUS and lethargy
- HYPERTHERMIA, coma, seizures (severe intoxication)
- death due to respiratory failure and cardiovascular collapse
Tx of aspirin toxicity?
- Emergency and supportive measure
- enhance elimination fo salicylates
- IV sodium bicarb with moderate intoxication
- hemodialysis with severe intoxication
Acetaminophen (APAP) toxicity and management?
At normal therapeutic dose small amt is excreted unchanged, a majority is excreted via conjugation to sulfate (30-40%) and glucuronide (50-60%), about 5-10% is metabolized by CYP450 2E1 to NAPQI which is a toxic and reactive metabolite. To get rid of the NAPQI, our body conjugates it with glutathione leading to cystine and mercapturic acid conjugates which are non-toxic and can be readily excreted in the urine. In the setting of a toxic dose of acetaminophen, conjugation pathways are saturated and a larger amt is going to be metabolized by CYP2E1 increasing amt of NAPQI. There is a depletion of conjugation of glutathione so rather than detoxifying NAPQI it accumulates in the hepatocytes leading to hepatotoxicity and cell death.
Acetaminophen toxicity is a major cause of acute liver failure and liver transplant in the US. In the setting of an acetaminophen poisoning, N-acetylcysteine can be administered which is a precursor for glutathione increasing conjugation ability as well as directly reacting with NAPQI detoxifying it.
Acetaminophen toxicity in the presence of acute alcoholism? What about chronic alcoholism?
Acute alcoholism inhibits CYP2E1 enzyme decreasing NAPQI accumulation and no toxicity. [PROTECTIVE]
Chronic alcoholism is an induces CYP2E1 enzyme increasing amt of NAPQI produced leading to increased cell death and possible fulminant hepatic failure. [DEADLY]
Effect of stimulants at normal vs higher doses?
Normal doses - euphoria, wakefulness, sense of power and well-being
Higher doses - agitation, acute psychosis, HTN, tachycardia, MYDRIASIS WITHOUT CYCLOPLEGIA, warm and sweaty skin, seizure, muscular hyperactivity leading to hyperthermia and rhabdomyolysis
How do you treat stimulant overdose?
- To enhance the rate of elimination of the amphetamines you want to acidify the urine with Ammonium chloride
- Phentolamine or nitroprusside for HTN
- IV benzo for seizures
- Neuromuscular paralysis with high body temp
Presentation of anti-cholinergic poisoning?
- skin flushing
- hyperthermia
- dry mucous membranes
- blurred vision and dilated pupils [mydriasis WITH cycloplegia]
- confusion and delirium
“red as a beet, hot as a hare, dry as a bone, blind as a bit, mad as a hatter”
How do you treat anticholinergic poisoning?
PHYSOSTIGMINE – b/c it can cross BBB – BUT DO NOT gives to a pt with TCA overdose b/c it can aggravate cardiotoxicity leading to heart block or asystole
For agitated pts you can administer benzodiazepines or antipsychotics.
B-blocker poisoning?
Block B1 and B2 receptors – most common is due to propranolol (non-selective) – at high doses it may block Na+ channels causing cardiac conduction block and is lipophilic so may enter NS leading to seizure and coma.
Presentation of B blocker poisoning- bradycardia and hypotension??
Presentation of partial agonist poisoning - tachycardia and HTN
Tx of B-blocker toxicity?
IV glucagon - increases cAMP levels at Gs activation raising bp and hr – it acts on its own receptors NOT B receptors
Calcium channel blocker toxicity?
L-type calcium channels lead to myocardial contractility and vasular SM contractility.
With CCB overdose…
- less muscle contraction leading to vasodilation leading to decreased pulsed pressure
- blocking Ca2+ channels at SV node, you get negative chornotropic effect (decreased HR)
- block calcium channels at AV node you have less stimulation of AV node leading to decreased conduction velocity (negative dromotropy)
- negative inotropy with decreased cardiac contractility
Calcium channel blocker management?
- IV Ca2+ for depressed cardiac contractility - barely any effect on nodal block or peripheral vascular collapse
- Glucagon and epinephrine - increase blood pressure in patients with refractory hypotension leading to HR increase
TCA toxicity?
- inhibition of NE and Serotonin re-uptake causing tachycardia, mild HTN, seizures
- Anticholinergic action - sedation and coma, peripheral anticholinergic effects (mydriasis, cycloplegia, dry skin, etc)
- direct a-adrenergic blockade - hypotension (b/c depolarizing block?)
- Quinidine-like (Na+) blockade of cardiac myocyte fast sodium channels – QRS widening, slowed conduction and depressed cardiac contractility
- QT prolongation due to inhibition of VG potassium channels (how??)
How do you manage a pt with TCA toxicity?
- SODIUM BICARBONATE - for quinine-like cardiac toxicity [by displacing TCA out of sodium channels]
- DO NOT GIVE physostigmine!!!
- Give NOREPINEPHRINE for the hypotension
MAOI toxicity?
Severe hypertension when tyramine-containing foods or drugs such as phenylpropanolamine or ephedrine are taken.
Tx with PHENTOLAMINE or LABETALOL for HTN – but labetalol is not the best one b/c it may stimulate the cardiac muscle.
MAOI-serotonin syndrome?
Hyperthermia
Muscle rigidity
MYOCLONUS
**selective stimulation of 5-HT2A and lesser so 5-HT1A
Tx - CYPROHEPTADINE (5HT2 receptor antagonist) with supportive management and benzos for seizures and agitation
Opioid toxicity?
Mild/moderate overdose - SMALL PUPILS, lethargy, decreased blood pressure and pulse rate
Higher dose - coma, respiratory depression, apnea leading to sudden death
Tx - NALOXONE or NALMEFENE
Theophylline toxicity and tx?
Acute normal manifestations - multisystemic response ranging from GI manifestations to metabolic effects (low K, low phosphate, elevated glucose, metabolic acidosis)
Acute Severe intoxication - seizures (most common cause of death), Hypotension and ventricular arrhythmias due to excessive stimulation
Chronic intoxication - cardiac dysrhythmias, NO GI disturbance or seizures
Tx - propranolol or esmolol for tacyarrhythias for B-adrenergic receptor blockers and benzos or barbiturates for seizures
Sulfonylureas and Meglitinide toxicity?
Hypoglycemia may occur – so administer IV dextrose (glucose) and octreotide (avoids any further release of insulin from B-cells)
Octreotide is a long-acting somatostatin analog that antagonizes pancreatic insulin release. Another drug, Diazoxide may be used as an alternative to octreotide, but octreotide is preferred for its safety and efficacy.
Neuroleptic malignant syndrome and management?
HYPERTHERMIA lead pipe muscle rigidity metabolic acidosis confusion **due to antipsychotic agents and metoclopramide
Management…
- discontinue all antipsychotics
- supportive therapy - tx hyperthermia with cooling measures, antipyretics do not seem to be very effective, give benzos (oral or IV lorazepam) to help with agitation
- pharmacological therapy - dantrolene, bromocriptine, amantadine are used but there is limited evidence of their effectiveness
Carbon monoxide poisoning?
CO - colorless, odorless, tasteless, non-irritating gas produced by incomplete combustion of any carbon-containing material.
Once CO is produced it tightly binds to hemoglobin iron forming carboxyhemoglobin (HbCO) reducing transport of O2 in the blood.
CO also shifts Hb to the relaxed state increasing its affinity for O2 – left shift on O2 saturation curve preventing release of O2 to tissues.
Tx - remove victim from area of exposure, administer 100% O2 or Hyperbaric O2
Ethanol toxicity and management?
- CNS depression - ethanol binds GABAa receptors in CNS increasing inhibitory effect, it is also an uncompetitive antagonist of NMDA receptors
- Hypoglycemia - due to impaired gluconeogenesis – depletion of NAD+ – raised NADH/NAD+ ratio
Management - supportive, IV dextrose, Vit B1 in chronic ethanol abuse
