Drugs presentation

On
Deriphylline

Presented to, Presented By,

Dr Suchita Yangad Mr. Angad Gaikwad

Assistant professor of Dr D.Y. patil 1st year NPCC student.

College of nursing Pimpri, Pune. Dr. D.Y. Patil college of

Nursing Pimpri, pune

Introduction

Theophylline is a medication used to treat asthma and chronic obstructive pulmonary

disease as a second-line drug. It is a bronchodilator. This activity reviews the indications,
action, and contraindications for theophylline as a potential agent in treating asthma and
chronic obstructive pulmonary disease. This activity will highlight the mechanism of
action, adverse event profile, pharmacokinetics, and drug interactions pertinent for
members of the interprofessional team in the treatment of patients with asthma and
chronic obstructive pulmonary disease.

Indications
Theophylline is a drug derived from methylxanthine (a purine derivative) and has smooth
muscle relaxant, bronchial dilation, diuretic, cardiac and central nervous system (CNS)
stimulant activities. It is naturally present in small amounts in tea and cocoa beans and
was initially extracted and synthesized in 1895 and used as a diuretic. In 1922, it came
out as a clinical treatment for asthma after identifying its bronchodilator effect. It is used
to treat various respiratory conditions that obstruct the airways, such as asthma and
chronic obstructive pulmonary disease (COPD).

Mechanism of Action

Theophylline relaxes the smooth muscles located in the bronchial airways and pulmonary
blood vessels. It also reduces the airway responsiveness to histamine, adenosine,
methacholine, and allergens. It exerts these effects mainly through two distinct
mechanisms:

 It acts as a competitive nonselective phosphodiesterase inhibitor (inhibiting

type III and type IV phosphodiesterase), which increases the concentration of
intracellular cAMP, activates protein kinase A, inhibits TNF-alpha, and
leukotriene synthesis, and also decreases inflammation and innate immunity.

 It is also a nonselective adenosine receptor antagonist. It acts on A1, A2, and

A3 receptors with almost the same affinity, which possibly explains
theophylline's cardiac effects. Adenosine-mediated channels also increase the
contraction force of diaphragmatic muscles by enhancing their calcium uptakex

 It inhibits nuclear factor-kappaB, preventing the translocation of the pro-

inflammatory transcription factor (NF-kappaB) to the nucleus, reducing the
expression of known inflammatory genes in COPD and asthma.

 Increases interleukin-10 secretion; interleukin-10 has broad anti-inflammatory

effects

 Increases histone deacetylase 2 through inhibiting phosphoinositide 3-kinase-

delta.

 Decreases poly (ADP-ribose) polymerase-1 (PARP-1)

  Increases apoptosis of inflammatory cells (T cells, neutrophils)

Administration

Theophylline can be used as an oral agent (rapid or slow-release tablets, solution, syrup,
or capsule) or in a more soluble form such as aminophylline (an ethylenediamine salt of
theophylline) that can be dosed orally or intravenously. Cautiously administer
theophylline in a patient who has consumed large amounts of foods or drinks with high
caffeine content, which could increase the risk of side effects of theophylline.

Intravenous (IV)

Patients can be administered IV theophylline for acute bronchospasm. Those who are not
currently taking theophylline should be given a loading dose of 5 to 7 mg/kg
intravenously, followed by a maintenance dose of 0.4 to 0.6 mg/kg per hour intravenously
to maintain serum concentrations at 10 to 15 mg/L.

Oral

Theophylline tablets are rapidly absorbed, but plasma concentrations show wide
fluctuations and are therefore not currently recommended. Several sustained-release
preparations that absorb at a relatively constant rate provide steady plasma concentrations
of the drug over a 12 to 24-hour period. It should be taken consistently with or without
food (as this helps maintain a more consistent serum drug concentration).

Dosing Considerations

 If administering aminophylline, the dose should increase by 25% (as

aminophylline is 79% to 86% theophylline).

 Dose calculations should use the ideal body weight.

 Aminophylline or immediate-release theophylline should be used for per-oral

loading.

Adverse Effects
Theophylline has a very narrow therapeutic window, and its interaction with various other
drugs has led to the limitation of its use. The serum theophylline concentrations require
monitoring directly to avoid toxicity as the adverse effects of theophylline are related to
its plasma concentration and have been observed when plasma concentrations exceed 20
mg/L. Some patients have also experienced adverse effects at low plasma concentrations.
The dose gradually increases until achieving therapeutic plasma concentrations. This
approach reduces side effects.

The most common side effects are nausea and vomiting, headache, increased stomach
acid secretion, and gastroesophageal reflux, which could be due to PDE inhibition. CNS
symptoms (irritability, lightheadedness, and dizziness) can also occur in patients.
In severe cases, seizures have also occurred. At high serum concentrations, adenosine A1-
receptor antagonism could lead to convulsions and cardiac arrhythmias

Contraindications

 Theophylline is contraindicated if the patient previously developed a

hypersensitivity reaction to the drug or any component of its formulation (such
as an allergy to corn-related products (in injection use only).

 Other contraindications include hypersensitivity to xanthine derivatives and

patients with coronary artery disease (where the cardiac stimulation effect of
theophylline might prove harmful).

Theophylline's pharmacokinetics involve absorption, distribution,

metabolism, and excretion:

 Absorption: Theophylline is well-absorbed from the gastrointestinal tract, with

peak plasma concentrations occurring within 1-2 hours after oral administration.
Food can affect absorption rates, with high-fat meals slowing absorption.

 Distribution: Theophylline distributes widely throughout the body, crossing the

blood-brain barrier and placenta. It binds extensively to plasma proteins, primarily
albumin.
  Metabolism: Theophylline undergoes hepatic metabolism primarily via
cytochrome P450 enzymes, predominantly CYP1A2, with minor contributions
from CYP2E1 and CYP3A4. This metabolism results in several metabolites,
including caffeine, 1-methylxanthine, and 3-methylxanthine.

 Excretion: Metabolites of theophylline are primarily excreted in the urine, with a

small percentage excreted unchanged. The elimination half-life of theophylline is
influenced.

Pharmacodynamics.

 Theophylline is a bronchodilator used primarily to treat asthma and chronic

obstructive pulmonary disease (COPD). Its pharmacodynamics involve inhibiting
phosphodiesterase, leading to increased levels of cyclic AMP within cells. This
results in smooth muscle relaxation, bronchodilation, and increased contractility of
the diaphragm. Additionally, theophylline can stimulate the central nervous
system, causing increased respiratory drive and decreasing fatigue in respiratory
muscles. It also has anti-inflammatory effects. However, it has a narrow
therapeutic window and can cause adverse effects if not monitored closely.

NURSING CONSIDERATION

 Assessment:

 Conduct a thorough assessment of the patient's medical history, including

allergies, comorbidities (especially liver or cardiac diseases), and current
medications.

 Assess baseline vital signs, respiratory status, and symptoms of underlying

conditions like asthma or COPD.

 Education: Educate the patient about the purpose of theophylline therapy,

including its mechanism of action and expected benefits.

 Emphasize the importance of adherence to prescribed dosing schedules and the

potential consequences of missed doses.
 Monitoring: Monitor vital signs regularly, especially heart rate and rhythm, as
theophylline can cause cardiac side effects such as tachycardia and arrhythmias.
Monitor for signs and symptoms of theophylline toxicity, such as nausea,
vomiting, tremors, and seizures.

 Drug Interactions: Assess for potential drug interactions, especially with

medications that affect theophylline metabolism, such as certain antibiotics (e.g.,
erythromycin, ciprofloxacin) and agents that inhibit or induce cytochrome P450
enzymes.

 Educate patients about avoiding excessive caffeine consumption, as caffeine can

increase the risk of theophylline toxicity.

 Assessment of Respiratory Status:Monitor respiratory status closely, especially in

patients with asthma or COPD, to assess the effectiveness of theophylline therapy.

 Evaluate the frequency and severity of respiratory symptoms and assess for signs
of exacerbation or improvement.

 Patient Counseling: Provide counseling on lifestyle modifications to optimize

theophylline therapy, such as smoking cessation and avoidance of triggers for
respiratory symptoms.

 Encourage patients to maintain regular follow-up appointments with their

healthcare provider to monitor response to therapy and adjust treatment as needed.