|Reviewed by NICU and Dept. of Pharmacy|
Dose and Administration1, 2
|Loading Dose||Maintenance dose|
|IV||20 mg/kg/dose- over 30 minutes||5mg/ kg/dose every 24hrs1,2,3|
|Oral||20 mg/kg/dose - give with feed||5mg/ kg/dose|
Note: Caffeine Citrate 20mg/ml is equivalent to Caffeine Base 10mg/ml
Caffeine is a member of the group of chemically related alkaloids known as methylxanthines. Almost all organ systems can be influenced by the methylxanthines, although the predominant site of activity involves the central nervous system and the cardiovascular system. Three major cellular actions of the methylxanthines have been suggested: translocation of intracellular calcium, increasing accumulation of cyclic nucleotides (particularly cyclic 3'S' AMP), and blockage of receptors for adenosine.
Pharmacological effects of caffeine include: stimulation of medullary respiratory centres, generalised enhancement of CNS cellular response to stimulation, increased heart rate, decreased peripheral vascular resistance, increased cerebral vascular resistance, smooth muscle relaxation, skeletal muscle stimulation, stimulation of gastrointestinal secretions, and diuresis. Caffeine may increase diaphragmatic contractility. The pharmacological mechanisms proposed for the alteration of neonatal apnoea include: increased sensitivity of medullary respiratory centre to CO2, increased afferent nerve traffic to brain stem, increased catecholamine response, stimulation of central inspiratory drive, improved skeletal muscle contraction, improved metabolic homeostasis, and improved oxygenation via increased cardiac output and decreased hypoxaemic episodes. Caffeine, when compared to theophyllines with equal efficacy, has fewer side effects. Caffeine has a wider therapeutic to toxic ratio and is administered once a day because of its long half-life. Serious problems are rare and only occur in large overdose but would include neurological abnormalities such as tremor, seizures and hypertension, cardiac abnormalities such as tachyarrhythmias. Side effects are rare at levels <400μmol/ml.
Oral administration results in very good bioavailability. There is little evidence that food delays absorption of caffeine. Caffeine is metabolised by the liver cytochrome oxygenase system which is induced by phenobarbitone and phenytoin. Levels may be increased by enzyme inhibitors such as cimetidine.