ISONIAZID

TOXICITY
Anita V. Ocampo-So, MD, DPBA, FPSA, MHA
May 2022
 OUTLINE
01 02
TRIAD PATHOPHYSIOLOGY

03 04 05
MANAGEMENT TREATMENT QUESTIONS
01.
Seizures TRIAD OF
ACUTE Metabolic
INH TOXICITY acidosis

Coma
02

PATHOPHYSIOLOGY
• Impairing the synthesis of gamma
aminobutyric acid (GABA).
• The toxicity results from depletion of
pyridoxine.
03 MANAGEMENT
HISTORY

Amount taken
• Seizure dose = 80-120 mg/kg

• Lethal dose = 6-10 gms

Early symptoms

Severe overdose
03 MANAGEMENT
HISTORY

PE Early signs

Severe overdose signs

Do complete neurologic examination

with fundoscopy
03 MANAGEMENT
HISTORY

PE Toxicologic exams
● Plasma INH levels
● Urine – 200 ml of metabolite
LAB EXAMS
Bedside toxicologic test

General examinations
03 MANAGEMENT
HISTORY

PE ABC of life support

Maintain vitals
NPO, start IVF
LAB EXAMS Insert NGT – gastric lavage
After gastric lavage, give sodium sulfate
GENERAL Repeat lavage after one hour if still no bowel movement
MEASURES
03 MANAGEMENT
HISTORY AMOUNT INGESTED UNKNOWN

Unavailable IV B6
PE
• Do lavage until return flow
is clear
LAB EXAMS • Give oral B6 = 120-240
mg/kg
GENERAL
MEASURES

SPECIFIC
MEASURES
03 MANAGEMENT
HISTORY AMOUNT INGESTED UNKNOWN

Unavailable IV B6 Available IV B6
PE
• Do lavage until return flow • 80-120 mg/kg IV bolus
is clear • B6 in combination with B1-
LAB EXAMS • Give oral B6 = 120-240 6-12 mixture 80-120
mg/kg mg/kg of B6
GENERAL
MEASURES

SPECIFIC
MEASURES
03 MANAGEMENT
HISTORY AMOUNT INGESTED UNKNOWN

Unavailable IV B6 Available IV B6
PE
• Do lavage until return flow • 80-120 mg/kg IV bolus
is clear • B6 in combination with B1-
LAB EXAMS • Give oral B6 = 120-240 6-12 mixture 80-120
mg/kg mg/kg of B6
GENERAL
MEASURES
If non-accidental, refer to a psychiatrist.
Maintenance = oral B6 10 mg/kg/day in divided doses for 3-6
SPECIFIC weeks
MEASURES
03 MANAGEMENT
AMOUNT INGESTED KNOWN
HISTORY
Unavailable IV B6

PE • Do lavage until return flow is

clear
• Give oral B6 2x the amount
LAB EXAMS of INH ingested

GENERAL
MEASURES

SPECIFIC
MEASURES
03 MANAGEMENT
AMOUNT INGESTED KNOWN
HISTORY
Unavailable IV B6 Available IV B6

PE • Dose of B6 is equal to the

• Do lavage until return flow is
dose of INH ingested
clear
• B6 in combination with B1-6-
• Give oral B6 2x the amount
LAB EXAMS 12 mixture in equal divided
of INH ingested
dosage, 15 mins apart, 1:1
ratio of INH ingested
GENERAL • B1 not to exceed 1g dose
MEASURES

SPECIFIC
MEASURES
03 MANAGEMENT
AMOUNT INGESTED KNOWN
HISTORY
Unavailable IV B6 Available IV B6

PE • Dose of B6 is equal to the

• Do lavage until return flow is
dose of INH ingested
clear
• B6 in combination with B1-6-
• Give oral B6 2x the amount
LAB EXAMS 12 mixture in equal divided
of INH ingested
dosage, 15 mins apart, 1:1
ratio of INH ingested
GENERAL • B1 not to exceed 1g dose
MEASURES
If non-accidental, refer to a psychiatrist.
SPECIFIC Maintenance = oral B6 10 mg/kg/day in divided doses for 3-6
MEASURES weeks
04. TREATMENT OF SPECIFIC PROBLEMS

1. ACIDOSIS

● If pH is 7.2 or patient is clinically acidotic, give

NaHCO3 1 mEq/kg or based on acid/base deficits if
with ABG.
● Repeat ABG after 30 mins and compute.
● Continue giving NaHCO3 until values are normal.
04. TREATMENT OF SPECIFIC PROBLEMS

2. MYOGLOBINURIA OR RHABDOMYOLYSIS

● Hydrate = 3-4 L/day

● NaHCO3 = 1 mEq/kg IV every 6 hours to maintain
urine pH ≥7.5
● Mannitol = 2.5 ml/kg IV every 6-8 hours
● Monitor CPK-MM serially
04. TREATMENT OF SPECIFIC PROBLEMS

3. PULMONARY EDEMA
● Furosemide 1 mg/kg/dose IV bolus
● Monitor urine output; if poor, do peritoneal dialysis

4. RENAL FAILURE
● Check urine output if less than 1 ml/kg

5. SEIZURES
● Diazepam
● Lorazepam
05
QUESTIONS
05 QUESTIONS

1. For patients on phenytoin for epileptic seizures, how

will you manage the patient?

● Give diazepam, 5mg IV for 3 doses; if no response,

give phenytoin 1.5-2.5mg/kg loading dose
● Maintenance dose: give 1mg/kg/dose every 8 hours
to avoid toxicity, because INH inhibits the
metabolism of phenytoin
05 QUESTIONS

2. What is the toxic dose of INH?

● 15-40 mg/kg

What dose will automatically cause seizure and coma?

● 80-150 mg/kg
05 QUESTIONS

3. What is the daily dose of INH which can lead to

toxicity if taken regularly and chronically?

● 10 mg/kg/day minimum dose

 THANK YOU!
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