Bronchodilator (Systemic Drug)
- Parenteral form of theophylline; bronchodilator drug with diuretic activity. Used short-term for bronchospasm and cardiogenic pulmonary edema. For oral use, see theophylline.
- Narrow therapeutic index in humans, but dogs appear to be less susceptible to toxic effects at higher plasma levels.
- Used in humans to ameliorate trouble breathing, shortness of breath and symptoms of asthma.1
- Cigarette smoking may affect the effectiveness of aminophylline2
- Numerous drug interactions.
Aminophylline is the parenteral form for administering theophylline. The theophyllines (eg, aminophylline, theophylline) are used primarily for their bronchodilatory effects. Although once used routinely in patients with myocardial failure and/or pulmonary edema, aminophylline is rarely recommended today for this purpose. Although theophyllines are still used, especially in animals with cough, they must be used cautiously because of their adverse effects and toxicity, and their use is generally limited to patients that have not responded to beta-agonist therapy.1 As with other theophyllines, aminophylline is indicated for the treatment of lung diseases such as asthma, chronic bronchitis, and COPD.
Aminophylline is used to treat bronchitis and other airway disorders, like asthma, in dogs, cats, and horses.
The theophyllines competitively inhibit phosphodiesterase, thereby increasing amounts of cyclic AMP (cAMP) that then increase the release of endogenous epinephrine. The elevated levels of cAMP may also inhibit the release of histamine and slow-reacting substance of anaphylaxis (SRS-A). The myocardial and neuromuscular transmission effects that theophyllines possess may be a result of translocating intracellular ionized calcium.
Theophyllines directly relax smooth muscles in the bronchi and pulmonary vasculature, induce diuresis, increase gastric acid secretion, and inhibit uterine contractions. They have weak chronotropic and inotropic action, stimulate the CNS, and can cause respiratory stimulation (centrally mediated).1
(Effects of aminophylline and mechanism of action) Aminophylline is distributed throughout the extracellular fluids and body tissues. It crosses the placenta and is distributed into milk (70% of serum levels). In dogs, at therapeutic serum levels, only about 7%-14% is bound to plasma proteins. The volume of distribution of theophylline for dogs has been reported to be 0.82 L/kg. The volume of distribution in cats is reported to be 0.46 L/kg and 0.85-1.02 L/kg in horses. Because of the low volumes of distribution and theophylline’s low lipid solubility, obese patients should be dosed on a lean body weight basis.
Theophylline is metabolized primarily in the liver (in humans) to 3-methylxanthine, which has weak bronchodilator activity. Renal clearance contributes only about 10% to the overall plasma clearance of theophylline. The reported elimination half-lives (mean values) in various species are ≈4.5-8.4 hours in dogs, 1 ≈7.8 hours in cats, ≈11 hours in pigs, and ≈11.9-17 hours in horses. In humans, there are very wide interpatient variations in serum half-lives and resultant serum levels. It could be expected that similar variability exists in veterinary patients, particularly those with concurrent illnesses.1
Contraindications / Precautions:
Aminophylline is contraindicated in patients that are hypersensitive to any of the xanthines, including theobromine or caffeine. Patients that are hypersensitive to ethylenediamine should not be given aminophylline.1
Theophyllines should be administered with caution in patients with severe cardiac disease, seizure disorders, gastric ulcers, hyperthyroidism, renal or hepatic disease, severe hypoxia, or severe hypertension (high blood pressure). Because it may cause or worsen preexisting arrhythmias, patients with cardiac arrhythmias should receive theophylline only with caution and enhanced monitoring. Neonatal and geriatric patients may have decreased clearances of theophylline and be more sensitive to its toxic effects. Patients with hepatic disease or congestive heart failure (CHF) may have prolonged serum half-lives of theophylline.1 The available literature suggests that women who are breast feeding may be given aminophylline.
Theophyllines can produce CNS stimulation and gastrointestinal irritation after administration by any route. Most adverse effects are related to the serum level of the drug and may be symptomatic of toxic blood levels; dogs appear to tolerate levels that may be very toxic to humans. Some mild CNS excitement and GI disturbances are not uncommon when starting therapy and generally resolve with chronic administration in conjunction with monitoring and dosage adjustments. Undiluted or rapid infusions of aminophylline can cause cardiac arrhythmias, hypotension, tremors, and acute respiratory failure.
Dogs and cats can exhibit clinical signs of nausea and vomiting, insomnia, increased gastric acid secretion, diarrhea, polyphagia, polydipsia, and polyuria. Side effects in horses are generally dose related and may include nervousness, excitability (auditory, tactile, and visual), tremors, diaphoresis, tachycardia, and ataxia. Seizures or cardiac dysrhythmias may occur in severe intoxications.1
The following drug interactions with aminophylline or theophylline have either been reported or are theoretical in humans or animals and may be of significance in veterinary patients.
The following drugs can decrease theophylline levels:
- BARBITURATES (eg, phenobarbital)
- CARBAMAZEPINE: May increase or decrease levels.
- CHARCOAL, ACTIVATED
- HYDANTOINS (eg, phenytoin)
- ISONIAZID: May increase or decrease levels.
- LOOP DIURETICS (eg, furosemide): May increase or decrease levels.
- SYMPATHOMIMETICS (eg, beta-agonists: albuterol, terbutaline)
The following drugs can increase theophylline levels:
- BETA-BLOCKERS (nonselective such as propranolol)
- CALCIUM CHANNEL BLOCKERS (eg, diltiazem, amlodipine)
- FLUOROQUINOLONES (eg, enrofloxacin, ciprofloxacin): If adding either, consider reducing the dose of theophylline by 30%. Monitor for toxicity and efficacy. Marbofloxacin reduces clearance of theophylline in dogs but not with clinical significance. In animals with renal impairment, marbofloxacin may interfere with theophylline metabolism in a clinically relevant manner.
- MACROLIDES (eg, erythromycin, clindamycin, lincomycin)
- THYROID HORMONES (exogenously administered)
Theophylline may decrease the effects of following drugs:
- BENZODIAZEPINES (eg, diazepam, midazolam)
- MACROLIDES (eg, erythromycin)
EPHEDRINE, ISOPROTERENOL: Toxic synergism (arrhythmias) can occur if theophylline is used concurrently with sympathomimetics (especially ephedrine); possibly isoproterenol.
KETAMINE: Theophylline with ketamine can cause an increased incidence of seizures.1
Laboratory Considerations - Theophylline can cause falsely elevated values of serum uric acid if measured by the Bittner or colorimetric methods. Values are not affected if using the uricase method. Theophylline serum levels can be falsely elevated by furosemide, phenylbutazone, probenecid, theobromine, caffeine, sulfathiazole, chocolate, or acetaminophen if using a spectrophotometric method of assay.1
Dogs and Cats - Adjunctive therapy of severe, acute pulmonary edema (rarely used today), cough, or bronchoconstriction (extra-label): 3 – 11 mg/kg IV (aminophylline injection) or IM (can cause pain) every 6-12 hours. Dogs may require the higher end of the dosage range and may be dosed every 6-8 hours. For cats, the low end of the dosing range is used and given every 12 hours. If effective, switch to oral therapy (theophylline) as soon as possible. When giving IV, do not push. Preferably administer over at least several minutes or as an infusion.
Horses - Adjunctive treatment of pulmonary edema or recurrent airway obstruction (RAO); (extra-label): 5 – 11 mg/kg IV every 8-12 hours. IV infusion should be in approximately 1 liter of IV fluids given over 20-60 minutes. Rarely recommended for use today. Consider monitoring serum aminophylline levels.1
NOTE: ARCI (RACING COMMISSIONERS INTERNATIONAL) CLASS 3 SUBSTANCE
Call your doctor (or veterinarian) or poison control authorities in the case of accidental exposure or exposure in humans with drug interactions risk.
1Plumb's Veterinary Drugs.2medlineplus.gov.