Xanthine derivatives include

Theophylline. Aminophylline, Oxitriphylline, Etophylline

Refer Aminophylline

Interacting drugs -summary

+ Theophylline

Benzodiazepines

sedative effects of benzidiazipenes may be antagonized by theophylline, although their pharmacokinetics do not appear to be altered. Co-admin may be beneficial in reversing sedation produced by benzodiazeines

Beta -agonists

theophyline act synergistically in vitro, an additive effect has also been demonstrated in vivo

Halothane

halothane with theophylline resulted in catecholamine -induced arrhythmias

Ketamine

and theophylline co-admin. has resulted in extensor-type seizures

Lithium

 lithium plasma levels may be reduced by theophyllines

Nondepolarizing  muscle relaxants

dose dependent reversal of neuromuscular blockade by theophylline may occur.

Probenecid

 may increase the pharmacologic effect of dyphlline due to decreased dyphylline renal excretion

Propofol

theophylline may antagonize the sedative effect of propofol

Ranitidine

 case reports suggest that theophylline plasma levels may be increased by ranitidine, possibly increasing pharmacologic and toxic effects (  occurance rare )

Tetracyclines

 incidence of theophylline adverse effects may possibly be enhanced by concurrent tetracyclines

Symptomatic relief of prevention of bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.

Xanthine derivatives include

Theophylline. Aminophylline, Oxitriphylline, Etophylline

Refer Aminophylline

New drugs approved For Marketing by Drug Controller General of India(DCGI )                                      during the period January 1988 to November 2014                                                                                     (Ref- IDMA Annual Publication 2015)

Neurotoxicity and seizures,cardiac arrhythmias.

CNS- irritability, restlessness, haedache, insomnia, reflux hyperexcitability, muscle twitching, convulsions.

GI - nausea, epigastric pain, hematemesis, diarrhea, rectal irritation, or bleeding,

Cardiovascular- papitations. tachcardia, extrasystoles, hypotension, ciruculatory failure, life-threatening ventricular arrhythmias.

Respiratory- tachypnea, respiratory arrest. Renal- proteinuria, potentiation of diuresis

Hypersens

Special precautions:

Elderly, children, acute pain, gradual withdrawal. Use with caution in- cardiac disease, hypoxemia, hepatic disease, hypertension, congestive heart failure, (CHF), alcoholism, elderly (particularlt males) and neonates.

GI- use cautiously in peptic ulcer. Local irritatin may occur,centally mediacted GI effects may occur with serum levels > 20mcg/ml.

Alcohol - addition of alcohol to liquid formulations is not necessary for absorption and may be potentailly harmful.

Warnings

Status asthmaticus-is a medical emergency and is not rapidly responsive to usual doses of conventional bronchodilators. Oral theophylline products alone are not appropiate for status asthmaticus.

Toxicitiy- excessive doses may cause severe toxicity , monitor serum levels to assure maximum benefit with minimum risk.

Pregnancy- give only if clearly needed.

Lactation- decide whether to discontinue nursing or discontiiue the drug taking into consideration the importance of the drug to the mother.

Children- there is evidence that the use of dosage recommendations for older infants and young children may result in the development of toxic serum levels.

Date of Approval       1993

Indications:

Symptomatic relief of prevention of bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.

Dosage:

Loading dose may be infused into 100 to 200ml of 5% dextrose injection or 0.9% sodium chloride injection. Do not exceed 25mg/ml infusion rate. Substitute oral therapy for IV aminophylline as soon as adequate improvement is acheived. Loading dose currently not receiving theophylline products- 6mg/kg.

Overdosage-

Symptoms Anorexia, nausea, vomting, nervousness, insomnia agitaton, irritability, headache, tachycardia, extrasystoles, tachypnea, fasciculation, tonic/clonic convulsions. . Convulsion or ventyricular arrhythmias may be the first signs of toxicity. Hyperamylasemia, simulating pancreatitis, has also been noted.

Treatment

1. If seizure has not occurred- Induce vomiting, even if emesis has occured spontaneously ipecac syrup is preferred

2. However, do not induce emesis in patients with impaired consciousness.

3. Take precautions against aspirations,especially in infants and children.

4. If vomiting is unsucessful or contraindicated ,perform gastric lavage (ofno value > 1 hour post ingestion)

5. Administer a cathartic (particularly for sustained- release preparations,sorbitol may be useful) and activated charcoal.

6. Prophylactic phenobarbital may increase the seizure threshold.

1. If seizure occurs- Establish an airway and administer oxygen.

2. Administer IV diazepam 0.1 to 0.3mg/kg upto 10mg.

3. Monitor vital signs,maintain blood pressure and provide adequate hydration.

1. Post seizure coma- Maintain airway and oxygenation.

2. Perform intubation and lavage instead of inducing emesis.

3. Introduce the cathartic and activated charcoal via a large bore gastric lavage tube.

4. Provide full supportive care and adequate hydration while the drug is metabolised.

5. If oral activated charcoalis inefective, charcoal hemoperfusion may be indicated.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

THEOPHYLLINE-

1. If GI upset occurs with liquid or non-sustained release forms, take with food.Take on an empty stomach at least 1 hr before or 2 hr after meals

2. Do not chew or crush enteric coated or sustained release tablets or capsules.

3. Take at the same time, with or without food each day.

4. Notify physician, if nausea, vomiting, insomnia, jitteriness, headache, rash, severe pain, restlessness, convulsions or irregular heart beats occurs.

5. Avoid large quanitities of beverages, such as tea, coffee, and cola drinks or large amounts of chocalate; these products may increase side effects.

6. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to aminophylline, caffeine, dyphylline, oxytriphylline, theobromine or theophylline. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

7. Diet- make sure your doctor knows that you are on any special diet. A high protein ,low carbohydrate diet may decrease the effect of effects of theophylline.

8. Pregnancy- use of theophylline during pregnancy may cause unwanted effects such as fast heart beat, jitteriness, irritation,gagging, vomiting, and breathing problems.

9.Breast feeding- theophylline, ephedrine, and phenobarbital pass into breast milk and cause unwanted side effects to nursing babies.

10.Children- newborn infants may be especially sensitive to the effects of theophylline.

11. Elderly- elderly people are more sensitive to the effects of theophylline

12. Other medicines - Tell your doctor if you taking Anticoagulants or Corticosteroids or Corticotropin - effects of these medicines may be decreased Beta-blockers- -use of his medicine may prevent either the beta-blocker from working properly.

MAOI- taking this medicine or within 2 weeks of taking MAOIs may increase the chance of serious side effects.

13. Other medical problems - Alcohol abuse or Fever or Liver disease or Respiratory infections - effect of theophylline may be increased Diabetes mellitus may make the condition worse

Diarrhea - absorption of theophylline may be decreased Enlarged prostrate or Heart or blood vessel disease or High blood pressure or Hyperacidity or Stomach ulcer or

14. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

15. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

16. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology

The methylxanthines(theophylline , its soluble salts and derivatives) directly relax the smooth muscles of the bronchi and pulmonary blood vessels) simulate the CNS, induce diuresis, increase gastric acid secretion, reduce lower esophageal sphinter pressure and inhibit uterine contractions

Pharmacokinetics

Theophylline is well absorbed from oral liquids and uncoated plain tablets; maximal plasma concentrations are reached in 2 hours. Xanthines are biotransformed in the liver.

Rate of absorption reduced, but not the extent.

Take on an empty stomah at least 1 hr before or 2hr after meals

Pregnancy

Not known whether theophylline can cause fetal harm when administered to a pregnant woman. Give only if needed.

Lactation:

Theophylline distributes into the breast milk. decide to administer the drug taking into consideration, the potential benefits againts the hazards to the nursing infant.