JURNAL TERKAIT KOMBINASI THEOPHYLLINE-EPHEDRINE

1. M. Weinberger et al.1975.Interaction of Ephedrine and Theophylline. Clin Pharmacol Ther.

17(5):585-92. DOI: 10.1002/cpt1975175585 (https://pubmed.ncbi.nlm.nih.gov/1092514/)

Interaction of ephedrine and theophylline

M Weinberger, E Bronsky, G W Bensch, G N Bock, J J Yecies
PMID: 1092514

Abstract
The effectiveness and safety of individualized theophylline doses administered as
such and in combination with ephedrine and hydroxyzine was investigated in 23
children with chronic asthma who received these medications and a placebo for 1 week
each, double-blind and in randomized sequence. Theophylline, determined by prior
clinical titration in each patient, averaged 7.3 mg/kg per dose administered every 6 hr, with
peak serum theophylline concentrations averaging about 16 mug/ml. Asthmatic symptoms
were controlled with theophylline. Ephedrine, alone or in combination, was relatively
ineffectual in these patients. None of the drugs given alone was associated with
significant adverse effects but both ephedrine-theophylline combinations (with and
without hydroxyzine) were associated with insomnia, nervousness, and
gastrointestinal complaints. Since the combinations were not significantly more
effective than theophylline alone, the apparent toxicity of these combinations
suggests a contraindication for the routine use of ephedrine with theophylline in
the management of chronic asthma.

2. RK Bush et al. 1978. A Comparison of a Theophylline-Ephedrine Combination with

Terbutaline. Ann Allergy. 41(1):13-7 (https://pubmed.ncbi.nlm.nih.gov/208429/)

A comparison of a theophylline-ephedrine combination with terbutaline

R K Bush, A M Smith, P G Welling, J C Alcala, T P Lee
PMID: 208429

Abstract
In a single-blind, crossover study 10 adult asthmatic patients received a theophylline-
ephedrine combination tablet (theophylline 90 mg, ephedrine 16 mg and
phenobarbital 25 mg in an immediate release layer and theophylline 90 mg and
ephedrine 32 mg in a sustained release layer) twice daily or terbutaline 5 mg three
times daily for two weeks. There was no significant difference in bronchodilator
response to a single dose of the study drugs on either the initial day of treatment or after
two weeks of continuous therapy. Mean increases in serum cyclic-AMP levels produced
by both drugs were not significantly different. Mean peak plasma theophylline levels were
2.9 +/- 1.3 microgram/ml following the initial dose and 7.3 +/- 3.4 microgram/ml after two
weeks of continuous dosing with the combination drug. No adverse effects on blood
pressure or pulse rate were observed to either drug. Overall, the incidence and
severity of reported side effects (tremor, nausea and nervousness) were less with
the theophylline-ephedrine combination.
3. WL Nyhan et al. 1974. Evaluation of oral bronchodilator therapy in Asthmatic Children.
The Journal of Pediatrics Volume 84:3,421-427 (https://www.jpeds.com/article/S0022-
3476(74)80732-8/pdf)

The bronchodilator efficacy of oral ephedrine and theophylline (as aminophylline),

separately and combined, was examined in a randomized double-blind study. Week-
long trials of five drug regimens were administered every 6 hours to 12 asthmatic children.
These regimens included conventional and “high” (approximately twice conventional)
doses of the two-drug combination in addition to a placebo and “high” doses of the
individual drugs. Efficacy was determined by symptom-medication comparisons and by
pulmonary function testing performed three times daily. Adverse drug effects were also
recorded and compared. Aminophylline (theophylline ethylenediamine) in “high” doses
(mean of 230 or 8.1 mg. per kilogram per dose) resulted in serum theophylline
concentrations averaging 13 μg per milliliter and 9μg per milliliter at 2 and 4 hours and
was highly effective in relieving signs and symptoms of asthma. The inclusion of
ephedrine resulted in no further benefit but did appear to increase the frequency of
adverse effects. The lower, more conventional doses of the ephedrine-theophylline
combination were ineffective in significantly altering the course of the disease.