THEOPHYLLINE

USES

CIRCUMSTAN
CES OF
POISONING
1.Accidental
Treatmen -can be
t of
ingested by
bronchia curious
l asthma toddlers due
and other to its general
syndrome availability.
s of
airway
2.Suicidal
obstructi
-by
on
adolescents
including or adults.
COPD in
adults
3.Unintenti
and
onal acute
bronchioli intoxication
tis in
on top of long
children.
term therapy
in asthmatic
patients due
to narrow
therapeutic
index of

TOXICOKINETICS
1.Absorption
-absorbed rapidly and
completely after oral
therapeutic
doses,reaching peak
serum concentration
within 2 hours .
-Sustained release
preparations reach
peak concentration
within 4-12 hours
after ingestion
2.Metabolism and
Excretion
-in plasma
,theophylline 60%
protein bound.
-in liver,it is
metabolized primarily
by hepatic p450
cytochrome oxidase
system.

PATHOPHYSIOLOGY
1.Competitive
antagonism of
endogenous
adenosine >
bronchoconstrictor,
anticonvulsant and
regulator of cardiac
rhythm.
2.Release of
endogenous
catecholamines

CLINICAL PICTURE OF ACUTE

POISONING
Serum theophylline concentration up to
20g/mL > toxicity
1.GIT - nausea,repeated
vomiting,diarrhea, abdominal pain,upper
GI bleeding.
2.CNS stimulation irritability,agitation,tremors,lethargy,seizu
res

Status epilepticus and coma

(prolonged seizures > rhabdomyolysis)
elevation of plasma
3.CVS
epinephrine and
- tachyarrhythmias(supraventricular
norepinephrine with
tachycardia)
resulting -adrenergic -hypotension > increased 2 adrenergic
receptor stimulation.
receptor stimulation with resultant
relaxation of arteriolar tone.
Theophylline induced
-cardiac arrest.
tachycardia,hypokalemi 4.Metabolic
a(intracellular shift)
-increased respiration > respiratory
,lactic
alkalosis > metabolic

theophylline.

-90% is metabolized
and 10% excreted
unchanged in urine.

acidosis,hyperglycemia. acidosis(compensation).
-increase level of endogenous
3.Direct stimulation catecholamines.
of respiratory centre
hypokalemia,hyperglycemia and
Increased rate and
hypercalcemia.
depth of breathing

THEOPHYLLINE
1-INVESTIGATION
A.Toxicological
-Serum level of theophylline (according to concentration , toxicity classified into mild ,moderate
and severe.
B.Non toxicological
-ECG, chest X ray ,measurement of arterial blood gases and acid bases status,
-serum electrolytes and blood glucose,myoglobin in urine,
-brain computed tomography ( for those who develop convulsions as seizures maye related to
cerebrovascular stroke )

MANAGEMENT

2-TREATMENT (ABCDES)
A.General supportive treatment (ABC)
B.Decontamination
-Gastric lavage
-Multiple dose activated charcoal is an effective method of enhancing the clearance of
theophylline especially in sustained release theophylline tablets.( 50g every 4 hour for 2 days )

< gut dialysis

-Concomitant use of charcoal with cathartic has been shown to be more effective in reducing
serum theophylline.
-syrup of ipecac is best avoided > can cause protracted vomiting.
C.Elimination
-Hemoperfusion. (haemodialysis considered when haemoperfusion not available)
D.Symptomatic treatment.
-convulsions > diazepam (5-10 mg IV).
-tachyarrhytmias >
beta blocker( propranolol)-may produce bronchoconstriction in susceptible individual.
Esmolol-short acting 1 specific adrenoreceptor antagonist > used succesfully for
reversal of tachycardia
-metabolic acidosis > IV NaHCO3.
-hypokalemia > potassium supplement.