EM Toxicology 9 - Antimicrobials Flashcards
obtain methemoglobin concentrations for patients with toxicity from
dapsone
chloroquine
sulfonamide
primaquine
MDAC is indicated in
symptomatic patients who have ingested dapsone or quinine
hemodialysis or hemoperfusion is effective at reducing concentrations of
dapsone
chloramphenicol
cefepime
pentamidine (possibly)
remarks with penicillins or cephalosporins
may produce seizures through GABA inhibition
amoxicillin overdose may produce
crystal-induced intertitial nephritis
hematuria
and renal failure
treatment is supportive with IV fluids
sulfonamide toxicity may result in
methemoglobinemia
treat with methylene blue
toxicity with this antimicrobial may reult in hypoglycemia
quinine (quinidine)
may also result in ototoxicity, ophthalmic toxicity
managed with
* MDAC
* sodium bicarbonate (target pH 7.55)
* dextrose
* octreotide
remarks on isoniazid toxicity
results in GABA syntehsis inhibition and functional deficiency of pyridoxine –> seizures
treat with
* benzodiazepines
* high-dose PYRIDOXINE
can cause pancreatitis
amoxicillin-clavulanate
and macrolides
both may also cause cholestatic hepatitis
may produce disulfiram-like reaction
cephalosporins with the N-methylthiotetrazole side chain, such as cefazolin and *cefotetan**
2 unique acute adverse reactions to procaine penicillin G
Jarisch-Herxheimer reaction
Hoigne’s syndrome
Jarisch-Herxheimer reaction
Can begin within a few hours following antibiotic tx of Lyme disease or early syphilis
Results from antigen released from lysed bacteria
Headache, fever, myalgias, rash
Usually limited to 24 hours
Hoigne’s syndrome
Begins within minutes after IM or IV injection of procaine penicillin G
Cause is unclear
Extreme apprehension, fear, hallucinations, illusions, hypertension and tachycardia, and seizures
Amoxicillin and ceftriaxone have been reported to produce a similar reaction
Fluoroquinolone toxicity
QT prolongation and subsequent torsades de pointe
in children, potential abnormality with developing cartilage and bone, although data suggest the risk is very low
in adults, tendon rupture has been attributed to fluoroquinolone use, with levofloxacin accounting for more than all others combined
discontinue the antibiotic in those who complain of painful or swollen tendons
linezolid toxicity
inhibits monoamine oxidase, and can lead to serotonin syndrome when used concurrently with other serotonergic meds
chronic therapy >28 days is associated with peripheral neuropathy and optic neuropatthy with loss of cenral vision and loss of color and visual acuity
also associated with pancytopenia
macrolides toxicity
m/c a/e: GI distress
most imporant a/e: QT prolongation with potential for torsades de pointes (lesser extent for azithromycin)
also associated with high-frequency sensorineural hearing loss
and rarely pancreatitis
antibiotics associated with rhabdomyolysis
trimethoprim-sulfamethoxazole
red man syndrome
vancomycin
rarely, this syndrome can cause seizures and CV collapse
most symptoms resolve within 15 minutes when the infusion is stopped
continue infusion at slower rate or with increased dilution or with pretreatment with diphenhydramine
chloroquine toxicity
Usually begins within 3 hours of ingestion with N/V and diarrhea
CV collapse may be precipitous with QRS widening and AV nodal blockade
Hypotension may be more severe than that seen with quinine overdose and is accompanied by respiratory depression and hypokalemia
aggressive supportive care is needed
early intubation, gastric lavage, deep sedation with BDZ
epinephrine to maintain SBP 100 mmHg
may cause hemolytic anemia and methemoglobinemia
primaquine, especially in a G6PD deficient population
quinine toxicity
cardiac toxicity
includes both sodium and potassium antagnism
which may result in widened QRS complex, QT prolongation and torasades depointes,
hypotension, syncopem and sudden death
blindness may result from serum levels >10-15 mcg/mL (31-46 mcmol/L)
deafness (tinnitus) and hypoglycemia (from hyperinsulinemia) may also occur
TX:
Mainstay is sodium bicarbonate to maintain serum pH 7.55
avoid class IA, IC, and III antidysrhythmic agents
Quinine overdose is one of the few drugs for which MDAC is truly indicated
anti-TB drug that carries high morbidity and mortality in overdose
ISONIAZID
overdose typically begin with ataxia, nausea, and mental status changes which may be seen as early as 30 minutes after ingestion
Symptoms may progress to the 3 classic features of isoniazid overdose
Seizures, Metabolic acidosis, Coma
seizures in isoniazid toxicity
typically follow acute isoniazid ingestions of greater than 20-30 mg/kg
GTC in nature
often refractory to standard anticonvulsive thearpy
MOA: functional def of B6 (pyridoxine) and inhibition of synthesis of GABA, the primary CNS inhibitory neurotransmitter
consider isoniazid overdose in patients with refractory seizures
management of isoniazid toxicity
Isoniazid-induced seizures are treated with a combination of benzodiazepines and pyridoxine
PYRIDOXINE
gram-for-gram equivalent to th amount of isoniazide ingested
- If quantity is unkonwn, give 5 g IV in adults and 70 mg/kg (max 5 g) in pedia
- administered at a rate of approx 1g IV every 2-3 minutes until the seizures stop or the maximum dose has been given
- after the seizures have ceased, the remainder of the pyridoxine dose should be given over the following 4-6 hours to limit recurrent seizures
- If seizures persist after the full dose has been given, it may be repeated.
pyridoxine may also assist in reversing isoniazid-induced coma
other remarks on isoniazid toxicity
phenytoin has no role in treating INH-induced seizures
there is little role for sodium bicarbonate tx of the metabolic acidosis resulting from INH toxicity
disposition of isoniazid toxicity
because most INH-induced toxicity occurs within 2 hours of ingestion, patients who remain asymptoamtic for 6 hours after ED presentation are safe for medical clearance
other anti-TB toxicity
Rifampin
infrequently causes severe toxictiy
most often assoc’d with GI symptoms
acute toxicity assoc’d with flushing, angioedema and neurologic effects (numbness, extremity pain, ataxia, weakness)
Ethambutol
primarily GI in nature
may cause unilateral or bilateral ocular toxcitiy (BOV, color perception disruption, loss of peripheral vision)
pyrazinamide is not associated with any toxic effects following acute overdose
oseltamivir toxicity
assoc’d with QT prolongation, but there’s no evidence the drug causes TDP or should be avoided in patients with congenital long QT syndrome
- benign QT prolongation
may cause neuropsychiatric effects including depression, agitation, and hallucination withint 24 hours of the first dose
