clinical toxicology exam 2

how does lithium distribute

rapidly absorbed initial distributed to extracellular fluid, and slowly distributes CNS, muscle, bone thyroid and kidney

what is lab monitoring for lithium

0.6-1 maintenance, 0.8-1.2 is for acute bipolar mania, >1.5 early signs of toxicity (tremor N/V vertigo confusion decrease deep tendon reflexes), >2.5 mEq/L severe neruological complication (seizure, coma) over 3.5 potentially lethal

what is acute toxicity

no prior burden of lithium and a toxic amount is ingested

what is chronic lithium toxicity

patient has existing body burden of lithium, serum concertation distributed and decreased lithium

what is acute-on- chronic toxicity

patient has existing body burden but ingest increased amount of lithium,

what causes decreased lithium elimination

increased age, decreased renal function, decreased sodium intake, dehydration, low output HF, NSAIDs Ace inhibitors, ARBs and thiazide diuretics

what are symptoms of acute lithium toxicity

early is acure GI AEs, mild is fine tremors muscle weakness and drowsiness, moderate toxicity is ataxia coarse tremors clonus hyperreflexia, agitation/restlessness, severe toxicity is seizures delirium profound confusions/coma myoclonus

how are GI symptoms and neuro symptoms correlate with different types of ingestions

acute Gi is severe Neuro is initially mild but may develop later level is not constant, chronic GI mild or absent SEvere neuro and poor corelating level, acute on chronic is severe GI severe neuron and levels are reliable

how is Lithium toxicity managed

assess airway emesis is common may lead to aspiration, minimal effects on breathing, drug formulation, Activated charcoal and SPS not recommended may use whole bowel irrigation, then give 0.9% NaCL as it promotes Li elimination increase renal perfusion avoid diuretics and sodium bicarb

when should hemodialysis be used for lithium toxicity

level over 4 with eGFR over 60 recommended if decreased level of consciousness, seizures, life threatening and dysrhythmias, is reasonable if over 5 regardless of renal function

what is long term complications of lithium toxicity

tremor , SILENT - syndrome of irreversible lithium effectuated neurotoxicity caused by chronic Li exposure symptoms are cerebellar dysfunction, cognitive impairment, EPS and autonomic dysfunction, CKD and nephrogenic diabetes insipidus AVP resistance in the kindey unable to concentrate urine stop drug

what endocrine disorders can be cause by chronic lithium toxicity

Hypothyroidism as it decreased T4 synthesis and responsiveness to T3, hyperthyroidism and hyperparathyroidism and hypercalcemia

what is other Lithium chronic complications

cardiovascular abnormalities T wave flattening or inversion prolongation of QT interval -, Hematologic leukocytosis, pregnancy increases congenital heart defects with in utero exposure, infants may also experience thyroid disease and neurotoxicity

what antipsychotic is the most prevalent overdose

Quetiapine

what are the effects of FGA

therapeutic effect on d2 antagonism reduce schizophrenia, EPS and hyperprolactinemia are AEs some can cause hypotension ,anticholinergic side effects, QRS-prolongation, QT prolongati3on

what is akathisia

due to neocortical D2 receptor antagonism is increased anxiety present hours to days can treat with benzos anticholinergic or dose reduction

what is dystonia

imbalance of dopaminergic and cholinergic transmission presents hours to days treat with benztropine diphenhydramine or benzos

what is psuedo-parkinsonism

happens weeks after taking anti psychotic, is due to post synaptic striatal D2 receptor antagonism, treat by dose reduction or alternative agent, anticholinergic and dopamine agonsit s

what is tardive dyskinesia

excess dopaminergic activity, upregulation of dopamine receptors taking months to years to present treat with anticholinergic and benzos

what is neuroleptic malignant syndrome (NMS)

lead pipe syndrome, high fever and autonomic dysfunction, caused by D2 receptor antagonism, pathways in striatum hypothalamus, onset is 2-10 days, treatment stop offending agent, cooling supportive care, benzos and maybe dopamine agonsit

what are the high potency FGAs

haloperidol, droperidol, prochlorperazine, and fluphenazine all are higher risk for EPS but lower risk for anticholinergic effects

what are the low potency FGAs

chlorpromazine and thioridazine less EPS but more anticholinergic and cardiac AEs

what are SGAs MOA

d2 antagonist and 5Ht2A antagonism less EPS but have some med specific AEs such as hypotension, anticholinergic effects, QRS prolongation, and QT prolongation

how dose acute overdose present for antipsychotics

depressed CNS, seizures, hypotension, tachycardia, QRS widening, QT prolongation, and Anticholinergic toxidrome

what is management of acute overdose for antipsychotic s

ABCs, supportive care, assess coingestion, GI decon?

what causes hyperthermia

increased heat production or impaired heat loss

what is serotonin toxicity

mild is akathisia tremor AMS, clonus moderate clonus sustained muscular hypertonicity and life threatening is hyperthermia

what is serotonin toxicity treated

cyproheptadine also give cooling and benzos

how is NMS treated

Bromocriptine cooling and benzos maybe dantrolene

what is malignant hyperthermia

is due to anesthetics and related to family history present as hot altered and hypertonia

how is malignant hyperthermia treated

dantrolene cooling and benzos

what is the best way to treat heat stroke patients

ice bath - is done by getting a big container filling it with ice and placing patient in it with a cover sheet, monitor temp and take out at 101 monito for recurrent hyperthermia rhabdo and coagulopathy

what determines the QRS complex

sodium

what determines the QT interval

Ca and K adn some mag

what effect do sodium channel blockers have on QRS

widen

what is given to treat QRS prolongation

sodium bicarb bolus to over come Na block if stable maybe sodium bicarb continuous infusion

what is a widen QRS

over 150

what is Qt prolongation treatment

avoid Qt prolonging meds avoid bradycardia replete electrolytes do not give sodium bicarb

what is QT prolonged

over 500

what are the secondary amines

Nortriptyline Desipiramine Amoxapine Maprotiline Protriptyline

what are the tertiary amines and why are they worrisome

Amitriptyline Imipramine Clomipramine Doxepin Trimipramine get metabolized into secondary amines meaning that there are multiple TCAs present

what is PK of TCAs

well absorbed larger VD high protein binding, and metabolized by hydroxylation and undergoes some hepatic recirculation and tetirary goes into secondary amine which have axctivity

what are the TCA toxicies

QRS widening, QT prolongation, hypotension, reflex tachycardia, seizures agitated delirium, CNS excitation

what is the cardiac effect of TCAs

sodium block causing QRS widening and potassium blockade prolonging QT interval, causes alpha 1 block leading to hypotension and reflex tachycardia (antimuscarinic also causes tachycardia) the tachycardia is protective of torsade

what are the neurologic effects of TCAs

anticholinergic effect is delirium sedation, coma, seizures through increase NE/5HT Na block and changes in gaba effect usually present within 1-2 hours , and signs of serotonergic excess -myoclonus rigidity

what are the benefits of SSRIs and SNRIs

relatively wide therapeutic window limits serious AEs in accidental overdose or minor to moderate intentional overdose patient needs to consume multiple months worth of meds to be harmful

what are the types of 5H receptors

5HT1 is releases serotonin, 5HT2, exciation of smooth muscle platelets and frontal cortex, 5HT3 vomiting, 5HT4, intestinal function and motility

what are SSRI/SNRI PK

onset vary are not equal citalopram and escitalopram have delayed effects such as seizures QT prolongation up to 16 hours after ingestion

what are the toxicity of SSRI/SNRI

potassium blockade causing QT prolongation, and inhibition of bioamines reuptake, seizures agitated delirium, serotonergic (myoclonus and rigidity) excess and hypertension —→ hypotension

what is bupropion toxicity

Very bad can happen with just a double dose Na blockade causing QRS prolongation (unresponsive to sodium bicarb), K blockade QT prolongation, inhibition of bioamines reuptake seizures (can be unresponsive to benzos) delirium, serotonin syndrome and tachycardia and effects can be delayed up to 24 hours after ingestion

what is bupropion treatment

hypotension give fluids QRS prolongation try sodium bicarb if unresponsive give lidocaine , QT prolongation replete MG, K and Ca, anticholinergic avoid anticholinergics maybe physostigmine, serotonin excess benzos and cool, seizures benzos barbiturates propofol

what is hallucination

a false perception that has no basis on the external environment

what are the two main synthetic hallucinogens

classic is agonism of serotonin 5HT2 receptors (LSD psilocybin), dissociative (PCP ketamine dextromethorphan) inhibition of glutamate at NMDA receptors

what are the general effects of hallucinogens

sympathomimetic signs, agitation, aggression, delirium, severe is psychosis, seizures coma, serotonin syndrome, excited delirium, rhabdomyolysis and multisystem organ failure

what is LSD

synthetic acts on 5HT2 receptor start 30-90 minutes last 6-12 hours, have visual and auditory hallucination enhanced emotion and dilated pupils increased HR, increase BP, sweating and mild tremors, toxicity is bad trips paranoia confusion, flashbacks and rarely cardiovascular instability, no physical but can be mental dependence

what is DMT

natural works on 5HT2A , rapid onset visual and auditory hallucination, last 15-60 minutes, smoked or vaporized can be ingested (ayahyasca combined with), toxicity increased BP and HR, psychological effects intense fear, confusion or disorientation, over dose can cause severe agitation or psychosis, no physical but psychological dependance

what is mescaline

natural phenethylamine mainly 5HT2A but also dopamine and norepinephrine, visual auditory hallucinations, anxiety paranoia, increase BP/HR, dilated pupils nausea tremors, begins 30-90 minutes last 6-12 hours, ingested as powder capsule or tea, toxicity nausea/vomiting, anxiety confusion panic attacks, no physical but psychological dependence

what is PCP

dissociative that acts on NMDA mainly as well as dopamine serotonin and norepi, dissociation feel out of body hallucination analgesic agitation, rapid onset last 4-6 hours dissociate can persist for longer, smokes ingestion injected or snorted, toxicity sever agitation volent behavior hypertension and tachy hyperthermia and psychosis can have physical and psychological dependance

what is ketamine

NMDA receptor antagonist, mainly dissociation as well as hallucination anesthesia and cognitive and motor impairment, rapid onset last 1-2 hours, injected snorted ingested, Toxicity severe agitation delirium HTN, respiratory depression cardiovascular instability and coma and bladder toxicity, can have physical and psychological dependance

kratom

low dose stimulant high dose opioid like analgesic can cause sedation, low dose increased alternes energy sociability euphoria high dose analgesia sedation, onset 15-30 minutes stimulate effect last 1-2 hours sedative 4-6, Toxicity overdose can lead to severe sedation respiratory depression seizures and coma, can have physical dependence like opioids and some psychological

Dextromethorphan

NMDA receptor, euphoric hallucination impaired motor function higher dose PCP like effect and opioid receptor agonist, effect within 30 minutes, toxicity tachycardia HTN, respiratory depression seizures rhabdomyolysis, hallucination paranoia agitation, high risk for serotonin syndrome, can have physical and psychological dependance has different plateaus

what is general hallucinogen treatment

serotonergic/sympathomimetics, avoid serotonergic al=gents active cooling and benzos, seizures benzos, rhabdo benzos and fluids

how does alcohol withdrawal work

with chronic alcohol consumption it increase GABA activity so when abruptly stop glutamate is highly increased leading to seizures

what are signs of alcohol withdrawal

tremor, sweating, HTN, tachycardia, agitation, anxiety insomnia, and seizures

what is a CIWA score

only given to a patient in alcohol withdrawal, under 10 is mild moderate is 10-18 and severe over 19 severe/complicated is signs of seizures or delirium

what is risk factors for severe withdrawal

history of severe withdrawal, multiple withdrawal episodes, seizure, comorbidity with brain, and co use of benzos or barbiturates, over 65 long duration of consumption, marked autonomic hyperactivity and presenting with a CIWA score over 10

what is severe alchol withdrawal

delirium tremens seizures and wenicke korsakoff (give vitamin B1)

what patient qualify for outpatient alcohol management

limited or mitigated risk factors, have done pervious ambulatory WD successfully, CIWA below 10, no history of complicated WD, good social support and no severe comorbidities

what are risk/benefits of ambulatory withdrawal

cost effective, reduce strain on hospital, reduce risk of infection, patient conform, risk is escalation of withdrawal, controlled substance prescription and returning home can be a trigger

what are the ambulatory alcohol QD meds

diazepam, lorazepam, chlordiazepoxide maybe GABA

what is inpatient withdrawal management characterisitcs

In moderate to severe WD Unsuccessful ambulatory attempt CIWA-Ar >10-15 Hx of Complicated WD/SZ Lack of support, housing, transportation Older age (65yo) Co-morbid (renal/liver disease)

what is fixed taper for alcohol WD

scheduled dosing to prevent alcohol withdrawal from working, pros is a consistent schedule and can get in front of withdrawal, cons may result in over medication,, and less flexible in adjusting to changing symptoms severity

what is symptom trigger alcohol WD dosing

base of CIWA score under 10 no meds give, 10-18 normal dose, 19 or above double dose, pros is tailored and addresses immediate needs, cons requires hourly monitoring, and more nursing time

what inpatient withdrawal treatment

benzos lorazepam 2-4mg per hour, diazepam 10-20 every hour, chlordiazepoxide 25-100mg per hour , if worse despite can give phenobarbital, if still not better intubate and propofol

what is phenobarbital dosing

IV/IM use PRN 130 to 260 may repeat every 15 to 20 minutes, or loading by 10 mg/kg over 15-30 minutes redosed same as the PRN max recommended is 15mg/kg

what nutrients are given to alcohol WD patients

B9, and B1

what are antiepileptics MOA

mainly Na channel inhibition (valproic inhibits NMDA and enhances GABA) lamotrigine effects some Ca

what antiepileptics are CYP inducers

carbamazepine and phenytoin

what is carbamazepine

MOA sodium channel inhibitor, is slowly absorbed but rapid distribution auto inducer CYP3A4, similar to TCA, toxicity CNS- Nystagmus ataxia seizures coma —Cardiovascular — tachycardia hypotension, myocardial depression rare QT QRS prolongation, —- unique in children dystonic reactions seizures choreoathetosis, —- chronic hyponatremia headache diplopia ataxia and leukopenia

how is carbamazepine toxicity treated

supportive care, benzos for seizures, hypotension fluids and pressors QRS over 100 sodium bicarb, hemodialysis for life threatening dysrhythmias and intractable seizures

lamotrigine

voltage gated sodium channel inhibition with some Ca, can have rash with rapid dose titration, can have DIHS, acute CNS is seizures CNS depressin agitation myoclonus and hyperreflexia, Cardiovascular is tachycardia HTN, and QRS prolongation

what is lamotrigine treatment

supportive care, seizures benzos, QRS widening sodium bicarb most likely wont work can use lipid emulsion, maybe hemodialysis

what is phenytoin

inhibition of sodium channels, zero order kinetics, CNS toxicity nystagmus, ataxia, lethargy. EPS symptoms, cardiovascular IV infuse slow 50mg/min can cause purple glove syndrome, chronic is gingival overgrowth, osteomalacia, megaloblastic anemia, decreased ADH and hepatoxicity

what is phenytoin treatment

supportive care, hemodialysis in severe CNS toxicity (coma , ataxia) Cardiovascular toxicity (IV admin) pause infusion give fluids and fosphenyotin consider electrolyte abnormalities — for chronic stop phenytoin and target supplementation

valproic acid

inhibits sodium channels, NMDA and GABA degradation, Acute CNS depression lethargy coma, cerebral edema 48-72 hours post ingestion, hypernatremia hypoglycemia anion gap metabolic acidosis, hyper ammonemia can be fatal, cardiovascular hypotension pancytopenia (present 3-5 days later)

how does VPA induced hyperammonemia encephalopathy happen

inhibition of CSP1 carnitine deficient inhibition of glutamate transport and mitochondrial dysfunction

what is VPA treatment

supportive care, hemodialysis if severe acidosis, intubation and VPA level over 850, levocarnitine for hyperammonemia maybe carbapenems

what is ethylene glycol

found in antifreeze, de-icing products, brake fluid and solvents, rapid absorption and distributed 0.6L/kg, metabolism is ethylene glycol gets broken down by alcohol dehydrogenase and aldehyde dehydrogenase into oxalic acid hippuric acid and hydroxy beta ketoadipic acid metabolism and eliminate in urine

how much is to much for ethylene glycol and toxicity

21ml, kidney injury (oxalic acid), AGMA (glycolic acid), hypocalcemia, and CNS (from calcium oxalate precipitation )

how is ethylene glycol diagnosed

EG concentration, Osm gap, Anion gap, and other stuff such as calcium oxalate crystal on UA, urine, fluorescence, hypocalcemia and kidney injury

what is the relationship between anion gap and osmol gap

osmol starts high after ingestion then goes low and anion gap start low then goes high

what is an normal osmol gap

normal is -14 to 10

what is ethylene glycol treatment

supportive care, fomepizole, pyridoxine, thiamine, dialysis

what does fomepizole do

stops ethylene glycol from getting metabolized into toxic acids

what does thiamine and pyridoxine do

make ethylene glycol into a less toxic metabolite

what is methanol

sources moonshine, windshield washer fluid, solid cooking fuels, model airplane fuel and photocopying fluids, rapidly absorbed is toxic the same was as ethylene metabolic

what is methanol toxicity

AGMA, visual impairment, basal ganglia toxicity, AKI, Rhabdo and pancreatitis

how is methanol diagnosis

ME concentrations, Osm gap, and Anion gap

what is methanol treatment

supportive care, fomepizole folate, dialysis, ETOH

what is Isopropyl alcohol

found in hand sanitizers rubbing alcohol, broken down into acetone, toxicity is ketosis without acidosis, CND depression hemorrhagic gastritis and treatment is supportive care maybe Fomepizole Dialysis Not really needed