It has recently been shown that the oxidative stress associated with cigarette smoke can inhibit the activity of HDAC2, thereby blocking the anti-inflammatory effects of corticosteroids.) Pharmacokinetics
Absorption
When theophylline is administered intravenously, bioavailability is 100%. Distribution
Theophylline is distributed in the extracellular fluid, in the placenta, in the mothers milk and in the central nervous system. The volume of distribution is 0.5 L/kg. The protein binding is 40%. The volume of distribution may increase in neonates and those suffering from cirrhosis or malnutrition, whereas the volume of distribution may decrease in those who are obese. Metabolism
Theophylline is metabolized extensively in the liver (up to 70%). It undergoes N-demethylation via cytochrome P450 1A2. It is metabolized by parallel first order and Michaelis-Menten pathways. Metabolism may become saturated (non-linear), even within the therapeutic range. Small dose increases may result in disproportionately large increases in serum concentration. Methylation to caffeine is also important in the infant population. Smokers and people with hepatic (liver) impairment metabolize it differently. Both THC and nicotine have been shown to increase the rate of theophylline metabolism. Excretion
Theophylline is excreted unchanged in the urine (up to 10%). Clearance of the drug is increased in children (age 1 to 12), teenagers (12 to 16), adult smokers, elderly smokers, as well as in cystic fibrosis, and hyperthyroidism.
Hypothermia, thrombocytopenia, leukopenia, hypocalcemia, and bleeding in the lungs are often results of IUGR.Infants with IUGR are at increased risk of perinatal asphyxia due to chronic hypoxia, usually associated with placental insufficiency, placental abruption, or a umbilical cord accident. This chronic hypoxia also places IUGR infants at elevated risk of persistent pulmonary hypertension of the newborn, which can impair an infants blood oxygenation and transition to postnatal circulation.If the cause of IUGR is intrinsic to the fetus, growth is restricted due to genetic factors or as a sequela of infection. IUGR is associated with a wide range of short- and long-term neurodevelopmental disorders. Cardiovascular
In IUGR, there is an increase in vascular resistance in the placental circulation, causing an increase in cardiac afterload. There is also increased vasoconstriction of the arteries in the periphery, which occurs in response to chronic hypoxia in order to preserve adequate blood flow to the fetus vital organs. This prolonged vasoconstriction leads to remodeling and stiffening of the arteries, which also contributes to the increase in cardiac afterload. Therefore, the fetal heart must work harder to contract during each heartbeat, which leads to an increase in wall stress and cardiac hypertrophy. These changes in the fetal heart lead to increased long-term risk of hypertension, atherosclerosis, cardiovascular disease, and stroke. Pulmonary
Normal lung development is interrupted in fetuses with IUGR, which increases their risk for respiratory compromise and impaired lung function later in life.