Pharmacologic agents including oral estrogens,alpha-blockers, sedative-hypnotics,antidepressants, antipsychotics, ACE inhibitors,loop diuretics, nonsteroidal anti-inflammatory drugs, and calcium channel blockers have been implicated to some degree in the onset or exacerbation of urinary incontinence.
US Pharm. 2014;39(8):24-29.
ABSTRACT: Urinary incontinence affects both men and women, and especially the elderly. The Agency for Health Care Policy and Research identified four types of urinary incontinence: stress, urge, mixed, and overflow. Pharmacologic agents including oral estrogens, alpha-blockers, sedative-hypnotics, antidepressants, antipsychotics, ACE inhibitors, loop diuretics, nonsteroidal anti-inflammatory drugs, and calcium channel blockers have been implicated to some degree in the onset or exacerbation of urinary incontinence. The pharmacist should consider urinary incontinence–inducing drugs when reviewing patient profiles.
In healthy humans, voiding occurs at intervals several times a day, even though the kidneys produce urine continuously. This means that the bladder must store urine for several hours, a feature that requires the musculature of the bladder-outflow tract to contract to generate resistance. Disturbances of this storage function of the bladder lead to urinary incontinence. A number of factors may be responsible, including disease and adverse effects of medical treatment.1
A number of medications have been proposed as possible causes of drug-induced urinary incontinence, including alpha1-adrenoceptor antagonists, antipsychotics, benzodiazepines, antidepressants, and drugs used for hormone replacement therapy.1 Since drugs are frequently metabolized and excreted in the urine, the lower urinary tract is particularly vulnerable to adverse effects. Furthermore, carcinogens or inflammatory agents in the urine are in close proximity to the epithelium for prolonged periods when they are stored in the bladder. The drugs may cause stress incontinence, urge incontinence, or overflow incontinence.2
This article discusses the different types of incontinence, their causes, and the possible mechanisms underlying incontinence resulting from medications.
The prevalence of urinary incontinence increases with age, with an overall prevalence of 38% in women and 17% in men. In women, the prevalence is about 12.5% in those aged 60 to 64 years and rises to about 20.9% in those aged ≥85 years. Furthermore, a higher prevalence has been noted in non-Hispanic white women (41%) compared with non-Hispanic black (20%) and Mexican-American women (36%).3 In a similar study, the prevalence of weekly incontinence was highest among Hispanic women, followed by white, black, and Asian-American women.4
In men, the prevalence increases with age, from 11% in those aged 60 to 64 years to 31% in those aged ≥85 years. The rate of incontinence in black men is similar to that for black women, but in white and Mexican-American men, the rate is 2.5 times lower than in women of the same ethnicity.3
Urinary incontinence may be underreported, owing to the embarrassing nature of the condition.
Types of Incontinence
According to the clinical practice guidelines issued by the Agency for Health Care Policy and Research (now called Agency for Healthcare Research and Quality), there are four types of incontinence: stress, urge, mixed, and overflow. Other guidelines identify functional incontinence as a fifth type.5-8 TABLE 1 describes the various types of incontinence in more detail, along with the usual approaches used in the management of each.5-10
Mechanisms of Urinary Continence
In healthy individuals, the urinary bladder senses the volume of urine by means of distention. Distention of the bladder excites afferent A-delta fibers (and C fibers, in a pathologic condition) that relay information to the pontine storage center in the brain. The brain, in turn, triggers efferent impulses to enhance urine storage through activation of the sympathetic innervation of the lower urinary tract (hypogastric nerve). These impulses also activate the somatic, pudendal, and sacral nerves.1
The hypogastric nerves release norepinephrine to stimulate beta3-adrenoceptors in the detrusor and alpha1-adrenoceptors in the bladder neck and proximal urethra. The role of beta3-adrenoceptors is to mediate smooth-muscle relaxation and increase bladder compliance, whereas that of alpha1-adrenoceptors is to mediate smooth-muscle contraction and increase bladder outlet resistance.1 The somatic, pudendal, and sacral nerves release acetylcholine to act on nicotinic receptors in the striated muscle in the distal urethra and pelvic floor, which contract to increase bladder outlet resistance.1
Efferent sympathetic outflow and somatic outflow are stopped when afferent signaling to the brain exceeds a certain threshold. At this point, the parasympathetic outflow is activated via pelvic nerves. These nerves release acetylcholine, which then acts on muscarinic receptors in detrusor smooth-muscle cells to cause contraction. A number of transmitters, including dopamine and serotonin, and endorphins are involved in this process.1
Pharmacologic Agents That Cause Urinary Incontinence
A variety of drugs have been implicated in urinary incontinence, and attempts have been made to determine the mechanism responsible based upon current understanding of the processes involved in continence and the transmitters that play a role. Each of the processes described previously can be manipulated by pharmacologic agents to cause one or more types of incontinence.
The drugs commonly pinpointed in urinary incontinence include anticholinergics, alpha-adrenergic agonists, alpha-antagonists, diuretics, calcium channel blockers, sedative-hypnotics, ACE inhibitors, and antiparkinsonian medications. Depending upon the mode of action, the effect may be direct or indirect and can lead to any of the types of incontinence. Taking these factors into account, it is important to consider a patient’s drug therapy as a cause of incontinence, particularly in new-onset incontinence patients and in elderly patients, in whom polypharmacy is common.11,12
On the other hand, a pharmacologic agent or any other factor that results in chronic urinary retention can lead to a rise in intravesical pressure and a resultant trickling loss of urine. In this way, drugs that cause urinary retention can indirectly lead to overflow incontinence.2
Alpha-Adrenergic Antagonists: As described earlier, the stimulation of alpha1-adrenoceptors by norepinephrine leads to increased bladder outlet resistance. It has been shown that alpha1-adrenoceptors influence lower urinary tract function not only through a direct effect on smooth muscle, but also at the level of the spinal cord ganglia and nerve terminals. In this way, they mediate sympathetic, parasympathetic, and somatic outflows to the bladder, bladder neck, prostate, and external urethral sphincter.13 Blocking these receptors with such agents as prazosin, doxazosin, and terazosin would therefore lead to reduced bladder outlet resistance and, accordingly, to incontinence.2 One study found that the use of alpha-blockers increased the risk of urinary incontinence in older African American and white women nearly fivefold.14 Another study showed that almost half of female subjects taking an alpha-blocker reported urinary incontinence.15Phenoxybenzamine, a nonselective, irreversible alpha-adrenoceptor antagonist, has been associated with stress urinary incontinence.1
It is useful to note that many antidepressants and antipsychotics exhibit considerable alpha1-adrenoceptor antagonist activity.1
Alpha-Adrenergic Agonists: Alpha-adrenergic agonists such as clonidine and methyldopa mimic the action of norepinephrine at receptors. In this way they may contract the bladder neck, causing urinary retention and thus overflow urinary incontinence.2,16-18
Antipsychotics: A number of antipsychotics have been associated with urinary incontinence, including chlorpromazine, thioridazine, chlorprothixene, thiothixene, trifluoperazine, fluphenazine (including enanthate and decanoate), haloperidol, and pimozide.19-24 Incontinence occurs over a broad range of antipsychotic dosages. Additionally, whereas some patients experience urinary incontinence within hours of initiating antipsychotic therapy, others do not experience incontinence for weeks after initiation. In most cases, the incontinence remits spontaneously upon discontinuation of the antipsychotic. Typical antipsychotics are primarily dopamine antagonists and lead to stress urinary incontinence, whereas atypical antipsychotics are antagonists at serotonin receptors.24 Antipsychotics also cause incontinence by one or more of the following mechanisms: alpha-adrenergic blockade, dopamine blockade, and cholinergic actions on the bladder.25 Owing to these complex drug-receptor interactions, a generalized description of how antipsychotics cause urinary incontinence cannot be given.1
If it is not possible to discontinue the antipsychotic, urinary incontinence caused by antipsychotics can be managed with a variety of pharmacologic agents. Desmopressin is perhaps the most effective, but also the most expensive, therapeutic agent available for this use. Other agents include pseudoephedrine, oxybutynin, benztropine, trihexyphenidyl, and dopamine agonists.25
Antidepressants: There are a number of classes of antidepressants, all with varying pharmacologic properties. This makes it difficult to generalize the underlying mechanisms that lead to urinary incontinence as a result of antidepressant use. However, all antidepressants result in urinary retention and, eventually, in overflow incontinence. Most antidepressants are inhibitors of norepinephrine and/or serotonin uptake. Some also act as antagonists at adrenergic, cholinergic, or histaminergic receptors at therapeutic doses.1
Diuretics: The purpose of a diuretic is to increase the formation of urine by the kidneys. As a result, diuretics increase urinary frequency and may cause urinary urgency and incontinence by overwhelming the patient’s bladder capacity. One study reported a link between diuretics and/or conditions associated with their use and urinary incontinence in community-dwelling women.26 In another study, the use of a loop diuretic with an alpha-blocker almost doubled the risk of urinary incontinence versus alpha-blockers alone, but no increased risk was noted when thiazide diuretics or potassium-sparing diuretics were added to the alpha-blockers.27
Calcium Channel Blockers: Calcium channel blockers decrease smooth-muscle contractility in the bladder. This causes urinary retention and, accordingly, leads to overflow incontinence.10
Sedative-Hypnotics: Sedative-hypnotics result in immobility secondary to sedation that leads to functional incontinence.10 Furthermore, benzodiazepines can cause relaxation of striated muscle because of their effects on gamma-aminobutyric acid type A receptors in the central nervous system.1,28
ACE Inhibitors and Angiotensin Receptor Blockers: The renin-angiotensin system exists specifically in the bladder and the urethra. Blocking angiotensin receptors with ACE inhibitors or angiotensin receptor blockers decreases both detrusor overactivity and urethral sphincter tone, leading to reduced urge incontinence and increased stress urinary incontinence.29 Furthermore, ACE inhibitors can result in a chronic dry cough that can cause stress incontinence. This was demonstrated in a female patient with cystocele who was receiving enalapril. The patient developed a dry cough and stress incontinence, which ceased within 3 weeks of discontinuing the ACE inhibitor.
Estrogens: One study showed that oral and transdermal estrogen, with or without progestin, increased the risk of urinary incontinence by 45% to 60% in community-dwelling elderly women.14 A summary of randomized, controlled trials also showed that the use of oral estrogen increased the risk of urinary incontinence by 50% to 80%.30
Hydroxychloroquine: Hydroxychloroquine has recently been identified as an agent that can induce urinary incontinence. There is currently only one report supporting this finding. In this report, a 71-year-old female patient developed urinary incontinence as an adverse reaction to hydroxychloroquine administered at therapeutic doses to treat rheumatoid arthritis. Urinary incontinence remitted with drug withdrawal and reappeared when the drug was readministered.31
A variety of drugs have been associated with urinary incontinence. This may be due to direct incontinence or overflow incontinence secondary to urinary retention. When reviewing patient profiles, pharmacists should take into consideration the use of oral estrogens, alpha-blockers, sedative-hypnotics, antidepressants, antipsychotics, ACE inhibitors, loop diuretics, nonsteroidal anti-inflammatory drugs, and calcium channel blockers that may lead to urinary incontinence. It is important to keep in mind that some incontinence patients taking these medications may be too embarrassed to discuss their condition voluntarily.
Alternate Remedies for Kidney Stones. Lemon Juice and Olive Oil. Sounds awful, doesn’t it? Apple Cider Vinegar. Makes your mouth pucker just thinking of it. Coke and Asparagus. Sounds interesting, doesn’t it? Lab Grade Chanca Piedra. Lab grade chanca piedra has shown high success rates in kidney stonetreatment.
Kidney stones are crystalline “stones” formed by dietary minerals in the urine. Most stones are made up of calcium, potassium, and several other minerals and electrolytes, but calcium appears to be the most common kind of kidney stone. Passing a kidney stone is a painful experience that few people would ever forget, and …
Jan 28, 2011 – Extracorporeal shock wave lithotripsy, in short, is when a targeted shock wave is sent through the body to break up stones. It seems that inversion therapy helps the body pass the brokenstones. I also recommend reading the book “The Green Body Cleanse” to learn how to select foods that support kidney …
Citric acid helps to dissolve kidney stones. Apple cider vinegar can help alkalize blood and urine and increase stomach acids to prevent the formation of new stones. In addition to flushing out the kidneys, apple cider vinegar can help ease pain caused by the stones.
Oct 16, 2014 – It’s on the “Top 10 Natural Ingredients” list for a good reason. Apple Cider Vinegar is an effective remedy for a long list of ailments, including kidney stones. Not only will ACV help to breakapart and flush out stones, regular consumption of around 2 tablespoons per day can help to prevent future occurrences …
Sep 16, 2017 – Apple cider vinegar again contains citric acid that may help dissolve calcium deposits. Two tablespoons of pure apple cider vinegar mixed with 8 oz of water may reduce the symptoms ofkidney stones and prevent their development. This mixture can be drunk several times a day and may be most effective …
Kidney stones are composed of salts that can build up in the body and cause extreme pain. Try these easy 5 Kidney Stone Natural Remedies For Fast Relief!
Jul 25, 2009 – Before I delve into the topic of kidney stones, I want to remind you that the intent and purpose of this video and article is to provide you with information based on my own experience as a practicing physician for more than 20 years. Then, using the forum below, called Vital Votes, you can add your own …
Jun 2, 2017 – Here are some natural treatments that may help prevent or soothe the discomfort ofkidney stones and facilitate the healing process. Anyone who has ever passed kidney stones can relate in excruciating detail just how painful that process can be. People suffering from this event often end up in the …
Take care of your immune system with sleep, nutrition and other remedies such as herbs.
Pulmonary–renal syndrome combines both diffuse alveolar hemorrhage (recurrent or persistent bleeding into the lungs) and glomerulonephritis (damage to the microscopic blood vessels in the kidneys in which people have body swelling, high blood pressure, and red blood cells in the urine).
Goodpasture’s Syndrome. Goodpasture’s Syndrome is an uncommon autoimmune disease that affects both the kidneys and the lungs. An autoimmune disease means that the immune system, which usually protects the body from infection, attacks healthy parts of the body by mistake.
In autoimmune disorders that involve the lungs, the immune system attacks and damages lung tissue. Different … Important lung autoimmune disorders include diffuse alveolar hemorrhage, which involves bleeding into the lungs, andpulmonary–renal syndrome, which involves bleeding into the lungs pluskidney dysfunction.
Nov 7, 2016 – Researchers do not fully understand why the immune system attacks collagen in the lungsand kidneys. Goodpasture syndrome can run in families. So some researchers believe it may have a genetic component. Other factors that may increase the risk of Goodpasture syndrome include: Exposure to certain …
Vasculitis is an autoimmune condition—a disorder in which the body’s immune system attacks the body’s own cells and organs—that involves inflammation in the blood vessels and can cause similarlung and kidney problems. Goodpasture syndrome is sometimes called anti-GBM disease. However, anti-GBM disease is …
It includes glomerulonephritis, bleeding in the lungs, and a problem with your immune system that causes it to attack the tiny filters in your kidneys and the tissue in your lungs. The damage to yourkidneys can lead to chronic kidney disease and kidney failure. If Goodpasture syndrome is not diagnosed and treated quickly, …
Aug 1, 2017 – Goodpasture syndrome is an autoimmune disorder. It occurs when the immune systemmistakenly attacks and destroys healthy body tissue. People with this syndrome develop substances that attack a protein called collagen in the tiny air sacs in the lungs and the filtering units (glomeruli) of the kidneys.
An autoimmune disorder is an illness in which the body begins to attack its own healthy cells, producing inflammation and an overproduction of collagen, a naturally occurring protein that helps make up connective tissue and maintain skin elasticity. While some autoimmune diseases attack a specific part of the body, many …
Goodpasture’s syndrome is an unusual autoimmune disorder that can cause lung disease and chronickidney disease (CKD). A healthy immune system produces antibodies to fight off germs and bacteria. In Goodpasture’s syndrome, the immune system makes antibodies that attack healthy protein called collagen in the air …
Jan 11, 2016 – Goodpasture syndrome is a rare condition that occurs when your immune system attacks the walls of your lungs and the tiny filtering units in your kidneys.
Signs and symptoms of chronic kidney disease develop over time if kidney damage progresses slowly. Signs and symptoms of kidney disease may include:
- Loss of appetite
- Fatigue and weakness
- Sleep problems
- Changes in how much you urinate
- Decreased mental sharpness
- Muscle twitches and cramps
- Swelling of feet and ankles
- Persistent itching
- Chest pain, if fluid builds up around the lining of the heart
- Shortness of breath, if fluid builds up in the lungs
- High blood pressure (hypertension) that’s difficult to control
Signs and symptoms of kidney disease are often nonspecific, meaning they can also be caused by other illnesses. Because your kidneys are highly adaptable and able to compensate for lost function, signs and symptoms may not appear until irreversible damage has occurred.
A complimentary alternative or medical doctor can help you find holistic healing ways. Knowing details of your health history will allow your health care professionals and you determine the course of action toward a healthier you.
Your determination to optimize your current health and your environment will have a greater impact on your success to achieving a healthier you.
If I become your health coach, you have to work with me to motivate yourself to wake up each day with the goal of achieving maximum health.
Examine the air your breath, the water or liquid drink you take, the time you sleep and for how long, your stress level, the texture of your skin, your eyes and your vowel.
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