Ibuprofen–a.k.a. Advil, Motrin, Nuprin, Medipren, Midol, Rufen– is an understated and remarkable medication, the most commonly used and prescribed drug of the non-steroidal anti-inflammatory drug (NSAID) class. It is a taken-for-granted, go-to medication that is used for a great variety of bodily aches and pains and issues. In addition to its effects on decreasing pain (analgesia), it also decreases inflammation (anti-inflammatory), and decreases fever (anti-pyretic). These three combined effects on pain, inflammation, and fever can positively influence many bodily ills, including an annoying symptom that bring patients into the urologist’s office: sleep-disruptive nighttime urination.
Ibuprofen works by inhibiting two key enzymes, proteins that function to accelerate chemical reactions. Inhibition of the cyclo-oxygenase enzyme leads to decreased prostaglandin synthesis, thus decreasing inflammation. Inhibition of thromboxane synthase enzyme leads to decreased thromboxane synthesis, decreasing platelet aggregation (clumping) and effectively inhibiting blood clotting.
Ibuprofen’s function is predicated upon decreasing the manufacture of prostaglandins. What are prostaglandins?
Prostaglandins are hormone-like substances first discovered in human in 1935 by a Swedish physiologist. In 1982, three biochemists shared the Nobel Prize in physiology and medicine for their work with prostaglandins. These chemicals drive the inflammatory process (literally a “flame” turned “inwards”)–characterized by redness, heat, pain and swelling— as they are powerful vasodilators that increase blood flow. Prostaglandins serve many different functions. Paradoxically, some are powerful vasoconstrictors, functioning to decrease blood flow and increase blood pressure. Certain prostaglandins play an important role in clot formation. Some play a role in ovulation and stimulate uterine muscle contraction and the induction of labor. Prostaglandins also function to inhibit the secretion of gastric acid by the stomach.
Trivia tidbit: Prostaglandins are so named because the Swedish physiologist who discovered them initially found them in semen and named them based upon his erroneous thought that they were produced by the prostate gland.
Many Uses of Ibuprofen
Ibuprofen is commonly used for inflammatory, musculoskeletal and rheumatoid disorders including aches and pain from headache, migraine, arthritis, acute and chronic dental and oral/facial issues, backache, menstrual cramps, soft tissue and bone injuries, sports injuries, fever reduction, and for post-operative and post-dental procedure pain relief.
Less Obvious Utilities
Patent ductus arteriosus (PDA): The ductus arteriosus is the blood vessel that connects the pulmonary artery to the aorta, bypassing the pulmonary blood vessels during uterine life (since the lungs are not needed until birth). In PDA, a condition not uncommon in premature infants, this bypass blood vessel fails to close following birth, causing heart failure. Prostaglandins are responsible for keeping the ductus arteriosus open and closure can be facilitated with prostaglandin inhibition via ibuprofen (NeoProfen).
Cystic fibrosis: To decrease inflammation and the influx of inflammatory white blood cells into the lungs.
Orthostatic hypotension: This is low blood pressure and light-headedness associated with standing up, a.k.a. postural hypotension. Ibuprofen helps induce sodium retention and prevents vasodilation.
Alzheimer’s disease: Ibuprofen has been reported to reduce the development of the neurodegenerative process.
Parkinson’s disease: Ibuprofen has been used to reduce inflammation and oxidative stress.
Certain breast cancers: Ibuprofen may help reduce the recurrence risk of hormone-receptor-positive breast cancer and may also reduce the risk of breast cancer metastasizing to lymph nodes in overweight women.
Ibuprofen should be avoided in patients with peptic ulcer disease, gastrointestinal perforation or bleeding, bleeding abnormalities (especially in patients who may be adversely affected by prolongation of bleeding time), and patients on anti-coagulants. Caution needs to be applied in using ibuprofen in patients with impaired kidney or liver function.
UROLOGICAL USE: Sleep Time Urinary Frequency
Urologists commonly prescribe ibuprofen for pain after surgical procedures as well as for inflammatory conditions of the genital and urinary tract. Aside from these uses, ibuprofen has been found beneficial to diminish nighttime urination.
Nighttime urination (nocturia) is one the most annoying urinary symptoms that patients suffer with. No one relishes awakening multiple times at night and having one’s sleep disrupted by the frequent need to urinate.
There are numerous causes of nighttime urination. One way of deconstructing nocturia is to distinguish full volume versus partial volume voids. This can be easily done with a 24-hour voiding diary. Full volume voiding (urine volumes 10 ounces or more) is appropriate, the bladder doing exactly what it is supposed to do—fill, store, let you know when it is full, and empty. The important question becomes why are the kidneys producing so much urine while sleeping?
Another way of deconstructing nocturia is to distinguish the location within the body that is the root cause of the issue, whether it is a prostate, bladder, kidney, heart, lower extremity, pituitary, sleep or other issue.
Common causes of full-volume nocturia are the following: over-hydration, particularly in evening hours; obstructive sleep apnea; age-related nocturnal defect in the secretion of anti-diuretic hormone or unresponsiveness of the kidneys to the action of anti-diuretic hormone; congestive heart failure; and peripheral edema caused by heart, kidney or liver impairment, nephrotic syndrome, malnutrition and venous stasis. (Peripheral edema is the accumulation of fluids in the legs. When lying down to sleep, the fluid returns to the intravascular compartment and is released from the kidneys as urine.)
On the other hand, causes of small-volume nocturia are the following: primary sleep disorders including insomnia, restless leg syndrome, narcolepsy, and arousal disorders (sleepwalking, nightmares, etc.); small bladder capacity: bacterial cystitis, bladder stones, bladder cancer, radiation cystitis, interstitial cystitis, overactive bladder, pelvic floor muscle tension myalgia, scarring, radiation, other forms of bladder damage; incomplete bladder emptying: prostate enlargement, scar tissue in the urethra, neurologic issues affecting bladder function, bladder prolapse; anxiety voiding; extrinsic compression on bladder: uterine fibroid, constipation, pelvic mass, pregnancy, etc.
Ibuprofen inhibits prostaglandins, which play a role in regulating bladder muscle tone and urination. Ibuprofen also has an effect on the kidneys in reducing the volume of urine produced while sleeping. Clinical trials have demonstrated efficacy and safety in the improvement of nighttime urination, which is often sleep-disruptive, specifically the reduction of the number of nocturnal voids.
Regardless of the underlying cause, ibuprofen helps reduce the number of nighttime voids. Clinical trials of ibuprofen plus Tylenol (a product called Advil Dual Action) have effectively and safely reduced nocturia. Its action may be on the basis of its direct effect on bladder and prostate cells, but perhaps also by moderating minor aches and pains that might be causing one to sleep lighter and be awakened more readily or for unknown reasons. For the short term, this can be a helpful means of lessening the number of times one has to awaken at night to urinate. Advil Dual Action (Acetaminophen 250 mg and Ibuprofen 125 mg coated caplets) can be purchased at any pharmacy and is inexpensive, a 144-count bottle at Walmart costing less than $15, or about 10 cents a pill. Caution always needs to be exercised when taking any medication, including Ibuprofen and Tylenol. It is not appropriate for any patient on an anti-coagulant or those with peptic ulcer disease or bleeding tendencies and is not intended for long-term use. It is certainly worth a try for those suffering with sleep-disruptive night time urinary frequency.