methyl alcohol, methylxanthine, analgesics, sedatives and psychotropic drugs

mechanism of toxicity of methanol

non toxic but toxicity arises from metabolites

methanol => formaldehyde => formic acid => CO2 and H2O

ADH, ALDH, Folate dependent

formic acid problems and kinetics

seever high anion gap(metabolic acidosis

mitochondrial toxicity

optic nerve damage

basal ganglia necrosis

kinetics: absorption peak in 30-60 mins,

half life 12-24 hrs(30-52 with ADH inhibition)

phases of methyl alcohol toxicity

1. early intoxication (0-12 hrs)

2. latent period(6-30 hrs)

3. systemic toxicity(12-24+ hrs)

major manifestations of methanol toxicity

visual: blurred vision, photophobia, blindness(6-8 hrs)

metabolic: metabolic acidosis, kussmal breathing, hyperkalemia

neurological: coma

tachypnea, tachycardia

dilated poorly reactive pupils, fundoscopy: optic disc hyperemia/edema, retinal edema

investigations for methanol toxicity

serum methanol level (20 mg/dl, severe 50 mg/dl)

ABG,

electrolytes

renal and liver function tests

serum glucose

ECG

fundoscopic examination: optic disc and retinal edema

CT/MRI

criteria of diagnosis of methanol

history of methanol exposure

elevated methanol level >20mg/dl

high anion gap metabolic acidosis + visual acuity

management of methanol

ABCD, iv sodium bicarbonate

antidotal therapy: fomepizole(4-MP): no CNS depression, easier to administer and monitor, no hypoglycemic risk

ethanol: cns depression, hypoglycemia, difficult to maintain levels, requires frequent monitoring

cofactor therapy:

1. folinic acid(enhance folate dependent metabolism of formic acid)

2. folic acid

3. thiamine

Hemodialysis: remove methanol and formic acid

supportive treatment: BZDs for seizures, optic neuritis high dose corticosteroids

indications for hemodialysis in methanol

1. methanol level >25mg/dl

2. severe acidosis

3. visual symptoms

4. renal failure

5. refractory electrolyte abnormalities

digitalis modes of toxicity

accidental poisoning

suicidal

chronic toxicity: renal and cardiac ds., inappropriate dosing, concurrent diuretic use, drug interactions

mechanism of action of digitalis

1. inhibition of Na-K pump

2. enhanced inotropy

3. inhibition of Na-K ATPase in skeletal muscle

4. vagotonic effects: bradycardia, various degrees of heart block

5. electrophysiological changes

important symptoms of digitalis

arrhythmia

hyperkalemia acute

hypokalemia chronic

yellow or yellow green colour vision

investigation of digitalis

serum electrolytes: hypomagnesemia, hypercalcemia, hyperkalemia(acute), hypokalemia(chronic)

digoxin level: normal 0.6-2.1 ng/mL

ECG:

renal function test

therapeutic and toxic ECG changes in digitalis

therapeutic: ST segment sagging

Toxic: bradycardia, heart block, atrial tachycardia, ventricular tachycardia, peaked T waves(hyperkalemia)

treatment of Digitalis

ABCD

stop digoxin medicine

continuous cardiac monitoring

decontamination; GL(dangerous, pre treat with atropine), MDAC(consider due to enterohepatic circulation)

antidote: digibind(onset:30-60mins, peak: 4-6 hrs)

supportive management:

bradycardia and heartblock: atropine, temporary pacemaker if Fab unavailable

ventricular arrhythmia : phenytoin, lidocaine, magnesium sulfate

hyperkalemia:insulin/glucose, sodium bicarbonate

digibind mechanism and indications

mech: Fab fragment bind free digoxin in serum and complex renally eliminated

indications:

1. serum digoxin level: 10ng/mL in adults and >5ng/mL in children 6 hrs post ingestion and 15 ng/mL at any time

2. Ingested dose: 10mg adults, 4 mg in children

3. hyperkalemia: K>5 mEq/L in acute toxicity

4. life threatening arrhythmia

5. hemodynamically significant bradycardia: unresponsive to atropine

avoid the following with digoxin toxicity

calcium prep.

calcium channel blockers

beta blockers

cardioversion

hemodialysis and hemoperfusion

beta blockers mechanism of action

1. comp inhibition of ß receptors

2. membrane stabilising effects

3. lipid solubility effects

4. peripheral effects: inhibit glycogenolysis

important symptoms of Beta blocker toxicity

CVS: bradycardia, hypotension, AV block, ECG, wide QRS complex, prolonged QT

seizures

hypoglycemia

bronchospasm

investigations in beta blocker toxicity

1. ECG

2. continuous cardiac monitoring

3. serum electrolytes: potassium may be elevated

4. serum glucose

5. ABGs: severe shock

6. renal function test

treatment of beta blocker toxicity

ABCD

decontamination: GL: 1-2 hrs pre treat with atropine, AC

antidote: glucagon

supportive management:

A. bradycardia and hypotension:

1. First line: IV fluids, Atropine

2. second line: Glucagon, IV calcium

3. third line: glucose and insulin

4. fourth line: vasopressors/inotropes: Epinephrine, norepinephrine, dopamine, dobutamine, lipid emulsion therapy

seizures: BZDs, check and correct glucose

wide QRS complex: sodium bicarbonate