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Analgesics for Renal Colics

Introduction
Stone disease is 3rd most common problems in urology, after urinary tract infection and benign prostate hypertrophy. High incidence in productive age, 30-50 years. Male is more vulnerable to have this disease.
It is estimated about 12% of population have this disease. It means stone disease is a major health problems in urology.

Pain in Stone Disease
Pain is very unpleasant experience for man, thus several practitioners include pain as the fifth vital signs. Proper management of pain may improve the quality of life.


Pain in Renal colic is one of the most sever forms of pain that person may experience. Renal colic is secondary to a ureteric calculus, that caused by ureteric smooth muscle spasm, oedema and inflammation at the level of the calculus, and increased peristalsis and pressure proximal to the calculus.
Or in the simple words, pain is caused by an obstruction of the ureter by the stone, thus promotes spasm of smooth muscle to passage the stone.
abdominal pain
adopted from http://shine.yahoo.com/channel/health/

Persistent obstruction of the urinary tract may lead to renal impairment. Within hours, the pressure gradient across the glomerulus equalises as pelvic pressure increases. In response, glomerular filtration and renal blood flow reduce. Unless the obstruction is relieved, renal impairment ensues.


The most effective pain relief for patients with complete ureteric obstruction is relief of the obstruction by spontaneous passage or removal of the stone by surgical ways.

Interesting facts that most of patients do not have complete obstruction, so are not at imminent risk of renal impairment. But, severity of pain is almost same with complete ones. So, for these patients proper pain management is most important than surgical removal of the stone.

Conventional analgesics
Opioid analgesics and NSAIDs remain the mainstay of treatment for acute renal colic.

Opioid analgesics, e.g. morphine and pethidine, are commonly used for the acute episode of renal colic. Because of its rapid onset of action and the advantage that the dose may be titrated to effect. However, prolonged use may cause dependence and tolerance. Side-effects are common, including nausea, vomiting, constipation and drowsiness, and larger doses can cause respiratory depression and hypotension.
Recently, several trials have found that opiates doesn't give good effects on ureteric tone or the side effects overtake the benefits. Opiates is to thought to increase the ureteric tone, that is conterproductive in acute renal colic.

Tramadol is an opioid analgesic with fewer opioid side-effects.Tramadol is as effective as morphine for moderate postoperative pain but it does appear to be less effective for severe acute pain. The usage of tramadol in acute renal colic episode is still debate-able and need to undergo further trials to prove its efficacy.

NSAIDs are known to be as effective as opioids at relieving the pain of acute renal colic. Eventhough opiods is better in early pain relief but there is no difference after 30 min periodes. The analgesic action of NSAIDs results from the inhibition of prostaglandin synthesis.
This action prevents the afferent arteriolar vasodilatation and increased vascular permeability which promotes a diuresis and raises renal pelvic pressure. It also reduces oedema, inflammation and ureteric muscular over activity.
Pain medication

There are many NSAIDs available; the main differences between them are the incidence and type of side-effects, predominantly gastric irritation and ulceration. Ibuprofen has the fewest side-effects and the lowest risk of
gastrointestinal effects, but has the weakest analgesic action. Naproxen and diclofenac provide stronger analgesia with a low incidence of side-effects. Indomethacin is equipotent to naproxen but with a higher incidence of side-effects, including headaches, dizziness and gastrointestinal disturbances.
But, prolonged used of NSAIDs also not good for kidney, since it disrupt renal autoregulation of renal blood flow and maybe a nephrotoxic agent.

Alternative analgesics drugs
Several studies has recommonded about the potential of antimuscarinic drugs usage to modulate ureteric activity. Antimuscarinic drugs are commonly used for treating smooth muscle spasm, predominately gastrointestinal.
Buscopan is an antimuscarinic drug which has been shown in trials can decrease human ureteric activity in 80% of subjects. Unfortunately, these
drugs are associated with significant side-effects, including dry mouth, facial flushing, dryness of the skin, photophobia, loss of accommodation, urinary urgency and retention, and constipation, and so their use is limited in renal colic.

Drotaverine, a phosphodiesterase IV inhibitor, has an antispasmodic action without the antimuscarinic side-effects. It is currently used successfully in many countries for treating renal colic. There were no serious side-effects. The minor side-effects included nausea, vomiting, vertigo and a transient decrease in blood pressure. However, there was no comparison with
conventional analgesia and so the relative efficacy is unknown.

Nifedipine (Calcium Channel Blocker) appears to be the most effective drug. Calcium is necessary to develop the action potential and contraction of the ureter. Calcium-channel blockers prevent calcium influx and so would be expected to have an inhibitory effect on ureteric function. Unfortunately, the findings don't support the theory, less patients having pain relief using nifedipine. But, nifedipine has the advantage in promoting spontaneous stone passage and decreasing the mean time to stone passage.
So, maybe nifedipine is potential drug in conservative therapy of stone disease with combination with another kind of analgesics.

Summary
Opiate analgesics and NSAIDs remain the most effective commonly used analgesics for treating renal colic. Because of the side-effect profiles associated with both these groups, alternative methods of treatment are sought.
Local active warming during the transfer to the hospital appears to be an effective method of providing analgesia and anxiolysis before arrival at the hospital.


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Aspirin as a new paradigm in Prostate Cancer

Important of Prostate Cancer
Prostate cancer is a malignant tissue growth that consists of cells from the prostate gland. Generally, the tumor usually grows slowly and remains confined to the gland for many years. But, some type of prostate cancer are more aggressive, thus are more rapid grow and spread, so give more significant shortening of life expectancy in men affected by them.
Healthy Men and his wife

Prostate cancer is the most common cancer in men and also the 2nd leading cause of death from cancer after lung cancer. In USA, based on American Cancer Society's data, it estimates about 192,280 new cases of prostate cancer would be diagnosed each year around USA and around 27,360 would die from it.
In USA, estimated lifetime risk of being diagnosed with the disease is 17.6% for Caucasians and 20.6% for African Americans. The lifetime risk of death from prostate cancer similarly is 2.8% and 4.7% respectively. From those numbers and data, we can say that prostate cancer has a significant impact on men health nowadays.


The Risk Factors
Just like other cancer, prostate cancer until know, doesn't have a certain cause. Because many factors are involved in it development. So, it's better to use the term of risk factor.
- Genetic, it can be denied that this factor has a major impact on cancer, because the cancer itself is a genetic disease. People with positive family history of prostate cancer have a higher risk of having prostate cancer in their lifetime.
- Age, increasing age is associated increasing incidence of cancer. Why? maybe it related to several factors such as accumulation of carcinogents, increasing error of cell replication, decreasing capability of repairing cell-damaged, etc.
- Hormone, for prostate cancer, testosterone has a major role. A high level of testosterone gives fuel for the cancer to growth and development.
- Some unproven risk factors such as smoking, obesity, environmental toxins are associated with increasing risk of prostate cancer.

Now, i will focus on the issue of usage of aspirin in treatment of prostate cancer patient.

Health News
On October 25th 2010, researcher from American Society for Radiation Oncology said that "Men with high-risk prostate cancer benefited from the aspirin."
Aspirin which is one of the most ubiquitous and pedestrian drugs, appears to be the proctective one's against the risk of dying for prostate cancer patient has not yet spread beyond the gland based on the new study.

"We show that patients taking anticoagulant [blood thinning] medication had better outcomes with regards to prostate cancer death and that this benefit
was most prominent in patients who had high-risk disease," said study lead author Dr. Kevin Choe at Monday ASTRO teleconference, a radiation oncologist with the University of Texas Southwestern Medical School in Dallas.

Aspirin was the one which seems to be the most benefit for prostate cancer patients compare to other the blood thinners that used in the study.
Aspirin cartoon

Our body coagulation system seems to be got an effect from the presents of cancer in some way.

"Cancer patients tend to develop clots in their legs and lungs more frequently and also patients who develop clots in their legs and lungs tend to develop cancer more frequently," Choe noted. "We hypothesized that anticoagulant medication may lower the chance of death from prostate cancer in men who have localized prostate cancer."

From the retrospective study of patients with localized prostate cancer that had been treated with surgery or radiation after follow-up about 7 years, there is a significant different of risk of death. The risk reduction is about 50%.

Also other potential benefit from blood thinner agent in prostate cancer patients is a better controlled of PSA (prostate-specific antigen) that indicates the growth of cancer cells.

The Explanation
During the process of metastasis or spreading, cancer cells are coated by platelets when they enter the bloodstream. This mechanism protects them from immune cells and also helps them stick to their next location. The blood-thinner agents may work by interfering with this process.

"It's premature to say that aspirin should be used in a standard-therapy way in all patients with prostate cancer," Choe said. "But we may expect to see this benefit in those who are taking aspirin for other [usually cardiovascular] reasons."
Prostate Cancer Examination

Conclusion
Prostate cancer is one of major men's health problems and associated with higher morbidity, mortality, and cost.
Recognizing the risk factors is very important in order to early prevention and early detection of prostate cancer.
Aspirin, one of the most ubiquitous, cheap, and pedestrian drugs offers us a new paradigm in cancer treatment. It lower the risk of death and better controlled of cancer growth when added to therapy program.
But, the evidence is not sufficient enough to give a recommendation, so it's needed to do more larger trials of aspirin in prostate cancer.


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