Neuro (pt 3/4) Methanol, Ethylene Glycol, Anti-Seizures, Anti-Psych Flashcards
What is Methanol?
-Used in the industrial production of synthetic organic compounds and as a constituent of many commercial solvents
-Absorbed through the skin, respiratory or GI tract
-Eliminated in humans by oxidation to formaldehyde, formic acid and CO2
-Metabolism is slow…6-30 hours before toxicity develops
What are the toxic metabolites that Methanol is oxidized to?
Formaldehyde, formic acid & CO2 = toxic metabolites
How long does it take for Methanol toxicity to develop?
6-30 hours
What are the mild characteristics of Methanol toxicity?
Inebriation, gastritis, elevated osmolal gap
What is the Osmolal Gap?
The difference between measured serum osmolality and calculated serum osmolality
-97% of patients will have OG in the range +10 to -10.
-The presence of low blood pH, elevated anion gap and greatly elevated OG is a medical emergency that requires prompt treatment
An Osmolal Gap value greater than ____ is considered a critical value or cutoff.
15
-The presence of low blood pH, elevated anion gap and _________ OG is a medical emergency that requires prompt treatment
A greatly elevated OG
What are the Severe characteristics of Methanol toxicity?
-Odor of formaldehyde on the breath
-Visual disturbances (most characteristic symptom)
-Metabolic Acidosis
-Can cause blindness
-Bradycardia, prolonged coma, seizures, resistant acidosis
-Fatalities attributed to sudden cessation of respiration
What is the treatment for Methanol Toxicity?
-Dialysis in severe cases (blood levels >50mL/dl)
-Support respiration
-Suppress metabolism of methanol by alcohol dehydrogenase
-Alkalization to counteract metabolic acidosis
(Bicarbonate)
-Meds: Fomepizole, IV Ethanol
What is Fomepizole?
-Alcohol dehydrogenase inhibitor
-Alcohol dehydrogenase is the enzyme responsible for methanol oxidation in the liver
-Approved for Methanol and Ethylene Glycol poisoning
-Rapidly induces its own metabolism by CYP450’s after 48 hours (Increase the dose)
Why is IV Ethanol utilized as an alternative to Fomepizole in the treatment of Methanol toxicity?
Because it has a higher affinity for alcohol dehydrogenase than Methanol (!!!!)
-Used In Methanol and Ethylene Glycol poisoning
-Methanol stays in primary form, doesn’t create toxic metabolites. Still has to be dialyzed off.
-Decreases the formation of methanol’s toxic metabolites
-Used as heat exchangers, in antifreeze formations, and as industrial solvents
-Metabolized to toxic aldehydes and oxalate
Ethylene Glycol
Describe the 3 stages of Ethylene Glycol Overdose.
First few hours – transient excitation followed by CNS depression
4-12 hours – severe metabolic acidosis develops from accumulation of acid metabolites and lactate
After 12 hours – delayed renal insufficiency follows the deposition of oxalate in renal tubules
-Oxalate can lead to crystal formation and kidney stones
What is the treatment for Ethylene Glycol Overdose?
Treatment the same as for Methanol Toxicity (still needs dialysis to pull off metabolites and offending agents)
A finite episode of brain dysfunction resulting from abnormal discharge of cerebral neurons.
-Aberrant signaling in the brain, can be due to disorders, tumors, high fevers, etc.
Seizures
A heterogenous symptom complex disorder (caused by several different factors) characterized as chronic recurrent seizures.
-Approx 1% of the world’s population
Epilepsy
What are the three different mechanisms of Anti-seizure medications?
1) Enhancement of GABAergic (inhibitory) transmission
2) Reduction of excitatory (usually glutaminergic) transmission
3) Modification of ionic conductance (usually K+ hyperpolarization to decrease neuronal firing)
Which anti-seizure drugs have presynaptic targets that diminish Glutamate release?
Na 1.6 voltage-gated sodium channels (carbamazepine, monohydroxy derivative [MHD], phenytoin, lamotrigine, and lacosamide)
K7 voltage-gated potassium channels (retigabine [ezogabine])
α2δ (gabapentin and pregabalin)
Which anti-seizure drugs have postsynaptic targets that diminish Glutamate release?
AMPA receptors (perampanel)
T-type Ca voltage-gated calcium channels (ethosuximide, dimethadione)
Kv7 voltage-gated potassium channels (retigabine [ezogabine]
Which anti-seizure drugs are positive allosteric modulators of synaptic GABA A receptors (promote inhibition)?
Phenobarbital
Benzos
Which seizure type classifications all get the same type of drugs?
Focal Aware, Focal impaired awareness, Focal-to-bilateral tonic-clonic seizure (formerly grand mal), Generalized tonic-clonic seizure (formerly grand mal), and Generalized absence seizures.
Which seizure type classifications each require specific medications?
-Myoclonic
-Atonic
-Epileptic Spasms
What is the Therapeutic Strategy for anti-seizure drugs?
-Use of a single drug is preferred (Fewer adverse effects using monotherapy)
-Multiple drugs can be used simultaneously for patients with hard-to-control seizures
-The therapeutic index for most anti-seizure drugs is low (Toxicity is common)
-Teratogenicity is controversial (Children born to mothers taking anti-seizure drugs have an increased risk of congenital malformations; Must minimize fetal exposure to anti-seizure drugs while ensuring that maternal seizures do not go unchecked)
-Avoid abrupt withdrawal (Increased seizure frequency and severity can occur with accidental or purposeful withdrawal of meds; If a patient is seizure free for 3-4 years, a trial of gradual discontinuance is warranted)
-Most newer drugs (after 1990) have a broader spectrum of activity and many are well tolerated (Newer drugs are preferred to the older ones)
Explain the pharmacokinetics of anti-seizure drugs.
-Well absorbed with approximately 80%-100% of drug reaching circulation
-Not highly protein bound (Except for Phenytoin(Dilantin), Tiagabine(Gabatril), and Valproic Acid (Valproate) )
-Cleared chiefly by hepatic mechanisms
C-onverted to active metabolites that are also cleared by the liver (CYP450 enzyme inducers!!!!)
-Plasma clearance is slow – anti-seizure drugs are considered to be medium to long acting (Some have half-lives longer than 12 hours)
