Aminophylline is a bronchodilator compound made of theophylline and ethylenediamine. It works by inhibiting phosphodiesterase and antagonizing adenosine receptors. This leads to bronchodilation, increased heart rate and contractility. It has a narrow therapeutic index and interactions with many other drugs. Common side effects include nausea, vomiting and arrhythmias at high doses. It is used for reversible airway obstruction but requires careful dosing and monitoring.

1. AMINOPHYLLINE
DR.ATHAR

2. INTRODUCTION
Aminophylline is a compound of the
bronchodilator theophylline with ethylenediamine in 2:1
ratio.
Theophylline is one of the three naturally occurring
methylated xanthine alkaloids caffeine,theophylline and
theobromine
The ethylenediamine improves solubility, and the
aminophylline is usually found as a dihydrate
Aminophylline tends to be less potent and shorter acting
than theophylline.

3. STRUCTURE
• 1,3-dimethyl-7H-purine-2,6-dione; ethane-1,2-
diamine

4. PREPARATIONS
Injectable: 25 mg/mL (theophylline equivalent = 19.7
mg/mL)

5. Tablets: 100 mg (theophylline equivalent =
78.9 mg ), and 200 mg (theophylline
equivalent=158 mg)
225 mg controlled released tablets
Oral liquid: 105 mg/5ml (theophylline
equivalent = 90 mg/5ml )

6. PHYSICAL PROPERTIES
• It is more soluble in water than theophylline.
• White or slightly yellowish granules or powder, having a
slight ammoniacal odor and a bitter taste.
• Upon exposure to air, it gradually loses ethylenediamine
and absorbs carbon dioxide with the liberation of free
theophylline.
• Its solutions are alkaline
• Insoluble in alcohol and in ether.

7. MECHANISM OF ACTION
 Competitive Nonselective Phosphodiesterase
Inhibitor
• Increase tissue concentration of cAMP causes
bronchodilation diuresis, CNSstimulation, cardiac
stimulation, and gastric acid secretion.
• Induces release of epinephrine from adrenal medulla
cells and promotes catecholamine stimulation
of lipolysis, glycogenolysis and gluconeogenesis

8.  Nonselective adenosine
receptor antagonist.
• Adenosine is an endogenous extracellular
messenger that regulate myocardial oxygen
needs.
• It increases coronary artery blood flow, slows
heart rate, block atrioventricular node
conduction, suppress cardiac automaticity, and
decrease β-adrenergic effects on contractility

9. • Adenosine also antagonizes chronotropic and
ionotropic effects of circulating catecholamines.
• Adenosine’s receptors are competitively
antagonized by methylxanthines such as
aminophylline
• Aminophylline competitively antagonizes the
cardiac actions of adenosine at the cell surface
receptors. Thus, it increases heart rate and
contractility

10. • At high concentration it stimulate the
Release of Ca+2 from sarcoplasmic
reticulum, specially in skeletal and cardiac
muscle
• Inhibits release of histamine and other
mediators from mast cells and activated
inflammatory cells.

11. PHARMACOLOGICAL ACTIONS
CNS - Stimulation of higher centre.
- also stimulate vagal,respiratory and vasomoter
centre
Heart -stimulation
heart rate-increased
BP-systolic-increased ,diastolic-decreased
Blood vessel-relaxation
Bronchi -dilation
Kidney -diuresis

12. PHARMACOLOGICAL ACTIONS
Skeletal.muscle -increased contractility
Gastric mucosa -irritation
-increased secretion of acid pepsin
BMR -increased

13. PHARMOKOKINETICS
• These drugs can be given orally, although
absorption may be slow and not as
effective as when given parenterally
• Distributed in all tissues-crosses placenta
and is secreted in milk.
• Extensively metabolised in liver by
demetylation and oxidation.

14. PHARMOKOKINETICS
• Metabolism: Children >1 year and Adults:
Hepatic; involves CYP1A2, 2E1 and 3A4;
forms active metabolites (caffeine and 3-
methylxanthine).
• Only 10% is excreted unchanged in urine

15. • Protein binding Only 60%
• Half-life elimination: Highly variable and dependent upon
age, liver function, cardiac function, lung disease, and smoking
history
At therapeutic concentration t1/2 in adult is 7-12 hours.
It is lesser in children and more in elderly and infant.
• Metabolising enzymes are saturable, t1/2 is prolonged with
higher doses as kinetics changes from first to zero order ,
plasma concentration therefore increase disproportionately.
• Theophyllin has a narrow margin of safety: therapeutic
concentration range is 10-20 mcg/ml.

16. DOSE
Loading dose:
6 mg/kg in 100 to 200 mL of IV fluid intravenously once over 20
to 30 minutes.
Maintenance dose (following loading dose):
Otherwise healthy nonsmoking adult: 0.7 mg/kg/hr continuous
intravenous infusion.
Young adult smoker: 0.9 mg/kg/hr continuous intravenous
infusion.
Patient with cor pulmonale or congestive heart failure: 0.25
mg/kg/hr continuous intravenous infusion.

17. Oral:
Loading dose: 6.3 mg/kg orally once
Maintenance dose (following loading dose):
Otherwise healthy nonsmoking adult: 12.5 mg/kg/day in
divided doses. Do not exceed 1,125 mg/day.
• Young adult smoker: 19 mg/kg/day in divided doses.
• Patient with cor pulmonale or congestive heart failure:
6.25 mg/kg/day in divided doses. Do not exceed 500
mg/day.

18. PEDIATRIC DOSE FOR
APNEA OF PREMATURITY
<= 4 weeks: (IV or oral, all dosages based on
aminophylline):
Loading dose: 5 to 6 mg/kg once - if IV, dilute in IV fluid
and give intravenously once over 20 to 30 minutes.
Maintenance dose: 3 to 8 mg/kg/day divided every 6 to
12 hours.

19. LIVER DOSE ADJUSTMENT
Loading dose: 6 mg/kg (patient not receiving
aminophylline or theophylline) diluted in IV fluid at a rate
not more than 25 mg/min.
Maintenance dose: 0.25 mg/kg/hr continuous
intravenous infusion.

20. CLINICAL USES
• Used as a bronchodilator in reversible airway
obstruction.
• May be used in cases of Pulmonary edema and
pulmonary congestion secondary to heart failure.
• Aminophylline is used to reverse dipyridamole or
adenosine based infusions during nuclear cardiology
stress testing.
• Aminophylline has shown some promise as a body fat
reducer when used as a topical cream (sometimes
referred to as "cutting gel").
• Aminophylline is also a treatment option for anaphylactic
shock

21. SPECIAL INDICATIONS
• PREGNANCY -category C by the FDA
-evidence of embryolethality and teratogenicity in
animals.
-use during pregnancy when there are no alternatives
and benefit outweighs risk.
• LACTATION – excreted in human milk and may cause
irritability or other signs of mild toxicity.
• PEDIATRIC USE - safe and effective for the approved
indications in children.

22. SIDE EFFECTS
Theophylline concentration <20 mcg/mL
• nausea
• vomiting
• headach
• insomnia
• diarrhea,
• irritability,
• restlessness
• fine skeletal muscle tremors,
• transient diuresis.

23. • In patients with hypoxia secondary to COPD, multifocal
atrial tachycardia and flutter have been reported at
serum theophylline concentrations ≥15 mcg/mL
• Theophylline concentration>20 mcg/mL
persistent vomiting,
cardiac arrhythmias,
intractable seizures which can be lethal.

24. CONTRAINDICATIONS
• Hypersensitivity to theophylline or
ethylenediamine

25. Special Precautions
 Neonates,
 Elderly,
 Lactation,
 Pregnancy,
 Cardiac/hepatic diseases,
 Peptic ulceration,
 Hyperthyroidism,
 Hypertension,

26. Special Precautions
 epilepsy,
 heart failure,
 chronic alcoholism,
 acute febrile illness

27. DRUG INTERACTIONS
• Aminophylline has been found to decrease the sedative
effects of propofol and decrease topiramate antiseizure
action.
• Has synergistic toxicity with sympathomimetics such as
ephedrine.
• Halothane - the risk of side effects such as irregular
heartbeat may be increased.
• Ketamine - risk of seizures may be increased.

28. • Adenosine, benzodiazepines (eg, diazepam, lorazepam
midazolam), lithium,or nondepolarizing muscle relaxants
(eg, pancuronium) - effectiveness may be decreased by
Aminophylline.
• Allopurinol, cimetidine, disulfiram, interferon alpha,
macrolide antibiotics (eg, clarithromycin, erythromycin),
methotrexate, oral contraceptives, quinolone antibiotics
(eg, ciprofloxacin), verapamil - risk of side effects of
Aminophylline may be increased

29. • Aminoglutethimide, barbiturates (eg,
phenobarbital),
beta-blockers (eg, propranolol),
carbamazepine,
hydantoins (eg, phenytoin), rifampin, or
sulfinpyrazone –
effectiveness of Aminophylline may be
decreased

30. OVERDOSE
• Symptoms of overdose can occur at usual prescribed
dosages of aminophylline.
• Symptoms: agitation, nausea, frequent vomiting, unusual
thirst, fever, ringing in the ears (tinnitus), fast/irregular
heartbeat, seizures, confusion, chest pain, agitated
maniacal behavior, palpitation and arrhythmias.
• Treatment is usually supportive and withdrawal of the
drug.
• Restoration of fluid and electrolyte balance is necessary.

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