RATIONALIZATION FOR USE OF PARACETAMOL AND IBUPROFEN IN COMBINATION OR AS ALTERNATIVE IN CHILDREN FOR FEVER “LATEST TREND OF HOSPITALS”

WHAT IS FEVER?

Fever, which means a body temperature above the usual range of normal. Causes of fever includes abnormalities in the brain itself (brain lesions), environmental condition as heatstroke, hard exercise, anemia (deficiency of red blood cells or hemoglobin), by toxic substances that affects temperature.

WHAT IS PYROGEN AND HOW IT CAUSE FEVER?

PYROGEN is a substance which rise the temperature of body by increasing the set-point of the hypothalamic temperature regulating centers and cause fever. It’s may be the metabolic products of microorganism (endotoxins from gram negative bacteria or lipopolysaccharide released from bacterial cell membrane) or many proteins, breakdown of proteins or substance which released from degenerating tissues of the body.

Some PYROGEN can act directly and immediately on the hypothalamic temperature regulating centers and rise the temperature of body immediately. Some function indirectly and require several hours of latency before causing fever especially by endotoxins of gram-negative bacteria. 

HOW ENDOTOXINS (PYROGEN) INCREASE TEMPERATURE?

When bacteria or break down products of bacteria are phagocytized by the blood leukocytes when presents in blood or tissues macrophages when presents in tissue or by large killer lymphocytes. After, digestion of these bacteria by defensive army of body (leukocytes, macrophages and lymphocytes), there is the release of a substance called interleukin-l which also termed as leukocyte PYROGEN or endogenous PYROGEN which in turn induce formation of prostaglandin especially prostaglandin E2 which in turn acts on hypothalamus to increase the body temperature.

WHAT IS PROSTAGLANDIN?

Prostaglandin are unsaturated fatty acids derivatives that act on the tissues in which they are synthesized and are rapidly metabolized to in active products at the site of action. Prostaglandin, histamine and serotonin are belonging to a group called autacoids. Autacoids are being formed by the tissues on which they act thus, they function as local hormone. They don’t circulate in blood in significant concentration. 

BIO SYNTHESIS OF THE PROSTAGLANDIN 

Phospholipid of tissue cell membrane released free arachidonic acid which is primary precursors of Prostaglandin mainly by the action of phospholipase A2 enzyme. From arachidonic acid through cyclooxygenase pathway (COX-1and COX-2 enzymes) prostaglandin and other derivatives are formed. Non-steroidal anti-inflammatory drugs by inhibiting cyclooxygenase enzymes blocked the formation of prostaglandin at the thermoregulatory centers in the hypothalamus and at peripheral target sites and exhibit their anti-inflammatory (reduces inflammation) action, analgesic and antipyretic (subsides fever)

DIFFERENCE BETWEEN PARACETAMOL AND IBUPROFEN

Paracetamol subside fever by inhibiting prostaglandin in the brain but it’s exact mechanism of action is unknown. It’s act as antipyretic and as mild analgesic. However. ibuprofen acts at all over body and block synthesis of prostaglandin. Its act as antipyretic, analgesic and anti-inflammatory drug which is plus point of drug and helpful in treating inflammatory condition. Paracetamol has no anti-inflammatory action.

COMBINATION OF PARACETAMOL AND IBUPROFEN OR AS ALTERNATE USE IN FEVER OF CHILDREN 

There is latest Trends in the hospital to relief children from the fever, health care practitioner recommends combine regimens of paracetamol and ibuprofen or alternate them. Despite the fact, both medications can be taken at same time and cause no harm to the child but studies show no benefit of using combination over monotherapy (means use of single agent either ibuprofen or paracetamol). To get relief from fever, use single agent therapy, hydrate child properly, dress child in light cotton dressing to allow exchange of heat and use cool dressing. Since both medications are available as over the counter so parents must be care full in using them and they should not be taken for more than 48 hours in combination or as alternative without visiting doctors. The adverse effect profile of combine regimens besides the others include vomiting which itself dehydrate child. However, in some cases child becomes miserable with fever and not taken fluid properly then by weighing risk to benefits ratio the combine regimens can be prescribed so child feel some comfort from fever and intakes fluid properly. In short, single drug should be prefer in febrile children. There’s no benefit of using combine regimens over monotherapy due to insufficient evidence. 

COMBINATION OF PARACETAMOL AND IBUPROFEN OR ALTERNATIVE USE IN RELIEVING PAIN IN CHILDREN 

As we already discussed, ibuprofen has anti-inflammatory properties while paracetamol lacking this property so either combination or alternate use of this regimens will complement each other and relief pain more effectively rather than mono therapy (single drug use). So, the children having pain with inflammation due to injury or others factor this regimen will be more effective. 

CAUTION WHILE TAKING THIS REGIME 

Paracetamol should be taken after every 4-6 hrs. Total 4 doses per day.

Ibuprofen should be taken after every 6-8 hrs. Total 3 doses per day.

Prolong use of ibuprofen will induce vomiting and irritate mucosal lining of stomach which is undesirable in children.