Theophylline; Uses, Dosage, Side effects, Drug Interactions

A methylxanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Mechanistically, theophylline acts as a phosphodiesterase inhibitor, adenosine receptor blocker, and histone deacetylase activator. As a member of the xanthine family, it bears structural and pharmacological similarity to theobromine and caffeine, and is readily found in nature, and is present in tea (Camellia sinensis) and cocoa (Theobroma cacao). A small amount of theophylline is one of the products of caffeine metabolic processing in the liver?.

Mechanism of action of theophylline

Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Indications of theophylline

• Apnea of prematurity
• Asthma, acute
• Asthma, maintenance
• Relaxing bronchial smooth muscle
• Increasing heart muscle? contractility and efficiency; as a positive inotrope
• Increasing heart rate: (positive chronotropic)
• Increasing blood pressure
• Central nervous system stimulatory effect mainly on the medullary respiratory center.
• Chronic obstructive pulmonary disease (COPD)
• Asthma
• Infant apnea
• Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth muscles and relaxes the cardiac muscle.
• For the treatment of the symptoms and reversible airflow obstruction associated with chronic? asthma? and other chronic lung diseases, such as emphysema? and chronic bronchitis?.

Contra Indications of theophylline

• Overactive thyroid? gland
• Hypothyroidism
• Diabetes
• Cystic Fibrosis
• High blood pressure
• Heart attack
• Angina
• Chronic heart failure
• Fluid in the Lungs
• Ulcer? from Stomach Acid
• Acute? inflammation of the liver
• Liver problems
• Seizures
• Fever for Many Days
• Fast Heartbeat
• Shock?
• Sepsis? Syndrome?
• Third trimester of pregnancy
• Tobacco smoking
• Stop Smoking
• Poisoning by Breathing Drug Theophylline
• Multiple Organ Failure
• Chronic Cannabis Smoker

Dosages of theophylline

Strengths: 100 mg; 200 mg; 400 mg/24 hours; 600 mg/24 hours; 125 mg; 300 mg; 450 mg;

Asthma – Acute

• Loading dose: 5 mg/kg loading dose (patient not receiving theophylline or aminophylline).

Maintenance dose

• Otherwise Healthy Nonsmoking Adult: 10 mg/kg/day. Do not exceed 900 mg/day.
• Otherwise Healthy Adult Smoker: 16 mg/kg/day.

Asthma – Maintenance

Loading dose

• 5 mg/kg loading dose (patient not receiving theophylline or aminophylline).

Maintenance dose

• Otherwise Healthy Nonsmoking Adult: 10 mg/kg/day. Do not exceed 900 mg/day.
• Otherwise Healthy Adult Smoker: 16 mg/kg/day.
• Patient with congestive heart failure? or cor pulmonale?: 5 mg/kg/day. Do not exceed 400 mg/day.

Pediatric Dose for Asthma – Acute

Loading dose

• If no theophylline has been administered in the previous 24 hours: 5 mg/kg loading dose to achieve a serum concentration of about 10 mcg/mL;

Maintenance dose

• less than 42 days: 4 mg/kg/day orally.
• 42 days to 181 days: 10 mg/kg/day orally. Alternate dosing: [(0.2 x age in weeks) + 5] x kg = 24 hour oral dose in milligrams.
• 6 months less than 12 months: 12 to 18 mg/kg/day. Alternate dosing: [(0.2 x age in weeks) + 5] x kg = 24 hour oral dose in milligrams.
• 1 year to 8 years: 20 to 24 mg/kg/day.
• 9 years to 11 years: 16 mg/kg/day.
• 12 years to 15 years: 13 mg/kg/day.
• 16 years or older: 10 mg/kg/day. Do not exceed 900 mg/day.

Pediatric Dose for Apnea of Prematurity

Manufacturer recommendations

• Loading dose: 4.6 mg/kg/dose

Maintenance

• Premature neonates: Post natal age less than 24 days: 1 mg/kg/dose every 12 hours
• Premature neonates: Post natal age 24 or more days: 1.5 mg/kg/dose every 12 hours
• Full term infants: Total daily dose (mg) = [(0.2 x age in weeks) +5] x (weight in kg); divide dose into 3 equal amounts and administer at 8 hour intervals

Side Effects of theophylline

The most common

• Headache
• irritability
• restlessness
• sleeplessness
• unable to sleep
• stomach pain
• diarrhea
• dizziness, drowsiness
• upper respiratory tract infection.

Common

• stomach pain
• nausea, vomiting
• diarrhoea.
• agitation, including aggressive behaviour and/or hostility
• irritability, restlessness, feeling anxious
• depression
• seeing, feeling or hearing things that are not there (also called hallucinations)
• dream abnormalities, difficulty sleeping
• sleep walking.
• muscle aches or cramps, joint pain
• stomach pain
• nausea, vomiting
• diarrhoea.

Less common

• Abdominal or stomach pain
• general feeling of discomfort or illness
• headache
• joint pain
• pain or tenderness around the eyes and cheekbones
• shortness of breath or troubled breathing
• sweating
• tightness of the chest

Drug Interactions of theophylline

Theophylline may interact with following drugs,suppliment & may change the efficacy of drugs

• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine,risperidone)
• antiseizure medications (e.g., clobazam,  phenobarbital, phenytoin,   valproic acid, )
• aripiprazole
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• baclofen
• barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
• benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• Calcium channel blockers, diltiazem, verapamil
• domperidone
• famotidine
• gabapentin
• ipratropium
• ketotifen
• levodopa
• macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
• magnesium sulfate
• methylphenidate
• mirtazapine
• Methotrexate
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, rasagiline, selegiline,tranylcypromine)
• quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
• selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine, citalopram)
• serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
• sotalol
• tapentadol
• thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, )
• thioridazine
• tolterodine
• tramadol
• trimethoprim
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
• “triptan” migraine medications (e.g., eletriptan, sumatriptan)
• tryptophan
• tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
• Zafirlukast

Pregnancy & Lactation of theophylline

FDA Pregnancy Category B

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

It is not known if orciprenaline passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

References