Use of antibiotic in common cold
Treatment with antibiotics for uncomplicated upper respiratory tract infections causes more harm than benefit. A systematic review of randomized trials in people with upper respiratory symptoms for less than seven days found that rates of persistence of symptoms was identical in subjects who received antibiotics as in those who received placebo.
Many patients and clinicians erroneously place considerable importance upon the color of nasal discharge when making decisions about antibiotic use. In fact, colored nasal discharge is a normal self-limited phase of the uncomplicated common cold. The systematic review cited above found that the relative risk for persistent acute purulent rhinitis was less in patients treated with antibiotic treatment compared to those receiving a placebo; however the increased risk of adverse effects in those receiving antibiotic outweighed the minimal effect of treatment.
Nasal cultures can theoretically identify the small subset of patients with common colds complicated by bacterial infections due to organisms such as H. influenzae, M. catarrhalis, or S. pneumoniae. However, such cultures require several days to return, and a proportion of patients with positive cultures will almost surely have coincidental colonization rather than true infection.
The potential benefit of such nasal cultures was examined in a double-blind, placebo-controlled trial involving 314 patients who presented with symptoms typical of the common cold symptoms. Subjects were randomly assigned to receive five days of treatment with amoxicillin-clavulanate (375 mg three times daily) or placebo. 72 of 300 patients who had nasal aspirates performed had negative bacterial cultures, 167 had cultures that were positive only for bacteria not responsible for respiratory infections, and 61 had cultures positive for H. influenzae, M. catarrhalis, or S. pneumoniae. Antibiotic therapy benefited only those in the last group; 27 percent of those in the latter group versus 4 percent of placebo-treated patients had better symptoms scores. Because the majority of cultures of nasal discharge taken from patients with colds are negative or reveal non-pathogenic bacteria, and because results of cultures are not immediately available to guide treatment, we believe that cultures of nasal secretions in patients with the common cold are cost-ineffective, impractical and unnecessary.
It is important to note that approximately 0.5 to 2 percent of adult patients with colds and influenza-like illnesses develop acute bacterial sinusitis.
Some experts have suggested that macrolide antibiotics may have a beneficial effect in the treatment of the common cold by reducing inflammatory mediators such as interleukin (IL)-6 or IL-8. However, a prospective randomized study involving 24 healthy volunteers who consented to experimental nasal inoculation with rhinovirus 16 showed no difference in intensity or duration of cold symptoms, weight of nasal secretions, decrease in nasal peak flow, or concentrations of IL-6 or -8 in nasal fluid in patients treated with clarithromycin versus trimethoprim-sulfamethoxazole.
So antibiotic are not effective in the treatment of the common cold and should not be prescribed and Symptomatic therapy remains the mainstay of common cold treatment.
Wednesday, May 11, 2011
sexual dysfunction associated with antidepressant
Treatment of sexual dysfunction associated with antidepressant:
Antidepressant that cause sexual dysfunction:
Selective serotonin reuptake inhibitors (SSRI): paroxetine, citalopram, escitalopram, fluoxetine, sertraline, fluvoxamine.
Serotonin-norepinephrine reuptake inhibitors (SNRI): Venlafaxine, Desvenlafaxine, Duloxetine.
SSRI and SNRI have been reported to reduce libido in women and men, to cause anorgasmia in women, and to increase ejaculation latency in men.
Treatment:
Step 1: Decreasing the dose of the SSRI and SNRI will sometimes decrease sexual side effects while maintaining antidepressant efficacy.
Step 2: Use of a second drug:
A number of drugs have also been investigated in combination with SSRIs to alleviate sexual dysfunction.
1- Phosphodiesterase-5 (PDE-5) inhibitors: Sildenafil 50 mg to start, adjustable to 100 mg before sexual activity improve erectile function, arousal, ejaculation and orgasm.
2- ginkgo biloba: In an open trial, 37 male and female patients with selective serotonin reuptake inhibitor (SSRI) associated sexual dysfunction were treated with ginkgo biloba extract. Significant improvement was noted after four weeks in 86 percent of patients.
Dose: Oral: 40-80 mg 3 times/day.
Antidepressant that cause sexual dysfunction:
Selective serotonin reuptake inhibitors (SSRI): paroxetine, citalopram, escitalopram, fluoxetine, sertraline, fluvoxamine.
Serotonin-norepinephrine reuptake inhibitors (SNRI): Venlafaxine, Desvenlafaxine, Duloxetine.
SSRI and SNRI have been reported to reduce libido in women and men, to cause anorgasmia in women, and to increase ejaculation latency in men.
Treatment:
Step 1: Decreasing the dose of the SSRI and SNRI will sometimes decrease sexual side effects while maintaining antidepressant efficacy.
Step 2: Use of a second drug:
A number of drugs have also been investigated in combination with SSRIs to alleviate sexual dysfunction.
1- Phosphodiesterase-5 (PDE-5) inhibitors: Sildenafil 50 mg to start, adjustable to 100 mg before sexual activity improve erectile function, arousal, ejaculation and orgasm.
2- ginkgo biloba: In an open trial, 37 male and female patients with selective serotonin reuptake inhibitor (SSRI) associated sexual dysfunction were treated with ginkgo biloba extract. Significant improvement was noted after four weeks in 86 percent of patients.
Dose: Oral: 40-80 mg 3 times/day.
TCA and managment of Chronic (prolonged) pain
TCA and managment of Chronic (prolonged) pain
Chronic pain:
Prolonged pain is the result of temporary or permanent changes in and around the peripheral and central nervous systems. Common changes are related to tissue injury, often mediated by inflammation. Tissue injury releases multiple mediators, which proliferate the pain alarm in complex cascades. The pain of inflammation and injury is
usually limited and resolves as the injury heals. However, inflammation and injury are always accompanied by changes in the peripheral and central nervous systems. Peripheral nociceptors (pain fibers) become sensitized and more readily transduce pain signals and may do so in response to a lower-intensity stimulus than before the injury(e.g. A striking example of sensitization is sunburned skin, in which severe pain can be produced by a gentle slap on the back or a warm shower) . This can result in continuous spontaneous pain, as well as pain upon movement or manipulation of the injured tissues (incident pain). Adjacent uninjured tissues are recruited by neurons in the spinal cord in a phenomenon known as secondary hyperalgesia. If these changes persist after the initial inflammatory response resolves, the pain becomes chronic. Prolonged pain can be the result of ongoing tissue injury with normal nociception or due to nerve injury with abnormal nociception (neuropathic pain). In inflammatory and neuropathic pain, reactions to mild stimuli are out of proportion to the stimuli. Such evoked stimulus induced reactions are termed allodynia, hyperalgesia, and hyperpathia.
Allodynia is pain caused by a normally nonpainful stimulus. An example is sunburn.
Hyperalgesia is an exaggerated painful sensation caused by a normally painful mechanical or thermal stimulus. For example, a gentle pinprick is usually barely painful but can be very painful in a hyperalgesic area. In this condition, the threshold of firing
for the dorsal horn neurons is lowered by the continuous input of spontaneously firing C-fibers. This may result in increased excitability of the central nervous system, a process that is broadly termed central sensitization. In other words, the dorsal horn neurons respond to normally painful inputs in a sensitized fashion, potentially manifesting as amplified pain sensitivity or expression. This may be seen as enlargement of the area in the periphery where a stimulus will trigger pain or sensation.
Hyperpathia is an abnormally painful and prolonged reaction to a stimulus. For example, a single pinprick may cause minimal pain, but with repetitive pinpricks patients describe the pain as explosive and worsening as time passes. The worsening pain represents either summation or after sensations. Summation is the perception of increasing pain or sensation to a fixed repetitive stimulus with no change in the stimulus pattern or intensity. After sensations are persistent painful sensations that are felt even after the stimulus is removed.
Role of depression: Because depression is the most common emotional disturbance in patients with chronic pain(85% of chronic pain patients have depression), patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness.
Tricyclic antidepressant (TCA):
TCAs (amitriptyline, imipramine, nortriptyline, desipramine) are extremely useful for the management of patients with chronic pain. Although developed for the treatment of depression (Their therapeutic effects are attributed to inhibition of norepinephrine and serotonin reuptake at synapses) , the tricyclics have a spectrum of dose-related biologic activities that include the production of analgesia in a variety of clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that tricyclic drugs potentiate opioid analgesia, so they may be useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options.
Painful Conditions that Respond to Tricyclic Antidepressants
Postherpetic neuralgiaa
Diabetic neuropathya
Tension headachea
Migraine headachea
Rheumatoid arthritisa,b
Chronic low back painb
Cancer
Central post-stroke pain
aControlled trials demonstrate analgesia.
bControlled studies indicate benefit but not analgesia.
The TCAs that have been shown to relieve pain have significant side effects. Some of these side effects, such as orthostatic hypotension, drowsiness, cardiac conduction delay, memory impairment, constipation, and urinary retention, are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics. The serotonin-selective reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor) and duloxetine (Cymbalta), which are nontricyclic antidepressants that block both serotonin and norepinephrine reuptake, appear to retain most of the pain-relieving effect of TCAs with a side-effect profile more like that of the serotonin-selective reuptake inhibitors. These drugs may be particularly useful in patients who cannot tolerate the side effects of tricyclics.
Chronic pain:
Prolonged pain is the result of temporary or permanent changes in and around the peripheral and central nervous systems. Common changes are related to tissue injury, often mediated by inflammation. Tissue injury releases multiple mediators, which proliferate the pain alarm in complex cascades. The pain of inflammation and injury is
usually limited and resolves as the injury heals. However, inflammation and injury are always accompanied by changes in the peripheral and central nervous systems. Peripheral nociceptors (pain fibers) become sensitized and more readily transduce pain signals and may do so in response to a lower-intensity stimulus than before the injury(e.g. A striking example of sensitization is sunburned skin, in which severe pain can be produced by a gentle slap on the back or a warm shower) . This can result in continuous spontaneous pain, as well as pain upon movement or manipulation of the injured tissues (incident pain). Adjacent uninjured tissues are recruited by neurons in the spinal cord in a phenomenon known as secondary hyperalgesia. If these changes persist after the initial inflammatory response resolves, the pain becomes chronic. Prolonged pain can be the result of ongoing tissue injury with normal nociception or due to nerve injury with abnormal nociception (neuropathic pain). In inflammatory and neuropathic pain, reactions to mild stimuli are out of proportion to the stimuli. Such evoked stimulus induced reactions are termed allodynia, hyperalgesia, and hyperpathia.
Allodynia is pain caused by a normally nonpainful stimulus. An example is sunburn.
Hyperalgesia is an exaggerated painful sensation caused by a normally painful mechanical or thermal stimulus. For example, a gentle pinprick is usually barely painful but can be very painful in a hyperalgesic area. In this condition, the threshold of firing
for the dorsal horn neurons is lowered by the continuous input of spontaneously firing C-fibers. This may result in increased excitability of the central nervous system, a process that is broadly termed central sensitization. In other words, the dorsal horn neurons respond to normally painful inputs in a sensitized fashion, potentially manifesting as amplified pain sensitivity or expression. This may be seen as enlargement of the area in the periphery where a stimulus will trigger pain or sensation.
Hyperpathia is an abnormally painful and prolonged reaction to a stimulus. For example, a single pinprick may cause minimal pain, but with repetitive pinpricks patients describe the pain as explosive and worsening as time passes. The worsening pain represents either summation or after sensations. Summation is the perception of increasing pain or sensation to a fixed repetitive stimulus with no change in the stimulus pattern or intensity. After sensations are persistent painful sensations that are felt even after the stimulus is removed.
Role of depression: Because depression is the most common emotional disturbance in patients with chronic pain(85% of chronic pain patients have depression), patients should be questioned about their mood, appetite, sleep patterns, and daily activity. A simple standardized questionnaire, such as the Beck Depression Inventory, can be a useful screening device. It is important to remember that major depression is a common, treatable, and potentially fatal illness.
Tricyclic antidepressant (TCA):
TCAs (amitriptyline, imipramine, nortriptyline, desipramine) are extremely useful for the management of patients with chronic pain. Although developed for the treatment of depression (Their therapeutic effects are attributed to inhibition of norepinephrine and serotonin reuptake at synapses) , the tricyclics have a spectrum of dose-related biologic activities that include the production of analgesia in a variety of clinical conditions. Although the mechanism is unknown, the analgesic effect of TCAs has a more rapid onset and occurs at a lower dose than is typically required for the treatment of depression. Furthermore, patients with chronic pain who are not depressed obtain pain relief with antidepressants. There is evidence that tricyclic drugs potentiate opioid analgesia, so they may be useful adjuncts for the treatment of severe persistent pain such as occurs with malignant tumors. TCAs are of particular value in the management of neuropathic pain such as occurs in diabetic neuropathy and postherpetic neuralgia, for which there are few other therapeutic options.
Painful Conditions that Respond to Tricyclic Antidepressants
Postherpetic neuralgiaa
Diabetic neuropathya
Tension headachea
Migraine headachea
Rheumatoid arthritisa,b
Chronic low back painb
Cancer
Central post-stroke pain
aControlled trials demonstrate analgesia.
bControlled studies indicate benefit but not analgesia.
The TCAs that have been shown to relieve pain have significant side effects. Some of these side effects, such as orthostatic hypotension, drowsiness, cardiac conduction delay, memory impairment, constipation, and urinary retention, are particularly problematic in elderly patients, and several are additive to the side effects of opioid analgesics. The serotonin-selective reuptake inhibitors such as fluoxetine (Prozac) have fewer and less serious side effects than TCAs, but they are much less effective for relieving pain. It is of interest that venlafaxine (Effexor) and duloxetine (Cymbalta), which are nontricyclic antidepressants that block both serotonin and norepinephrine reuptake, appear to retain most of the pain-relieving effect of TCAs with a side-effect profile more like that of the serotonin-selective reuptake inhibitors. These drugs may be particularly useful in patients who cannot tolerate the side effects of tricyclics.
sleep disorder
What is insomnia and how we can treat it without medication:
Humans typically have 4 to 6 cycles of Nonrapid eye movment (NREM) and rapid eye movment (REM) sleep each cycles lasting 70 to 120 minutes usually there is progression through four stages of NREM sleep which are befor first REM period.
The stages of NREM are:
Stage 1: transitional state which is the stage between wakefulness and sleep
Stage 2: 50% of sleep time is spent in these stage , sleep here is light sleep
Stage 3 & 4: deep sleep (delta sleep i.e., slow-wave sleep)
These stages categorized using sleep EEG
After the four stages then comes the REM period (rapid eye movment): these period neither light nor deep sleep it is chractrized by the body being more physiologically active than during other sleep stages while skeletal muscles are actively inhibted.the first REM period lasts 5-7 minutes, the sleep cycles repeats every 90-120 minutes, with each progressive REM period becoming longer and the time in deep sleep becoming shorter.
Insomnia :
defention of insomnia: in insomnia patients complain of difficulty falling asleep, difficulty maintaining a sleep (nocturnal awakening), not feelling rested in spite of a sufficient opportunity to sleep ( poor quality of sleep), or early morning awakening.
causes of insomnia:
Situational
Work or financial stress, major life events, interpersonal conflicts Jet lag or shift work.
Medical
Cardiovascular (angina, arrhythmias, heart failure), Respiratory (asthma, sleep apnea), Chronic pain, Endocrine disorders (diabetes, hyperthyroidism), GI (gastroesophageal reflux disease, ulcers), Neurologic (delirium, epilepsy, Parkinson’s disease), Pregnancy
Psychiatric
Mood disorders (depression, mania), Anxiety disorders (e.g., generalized anxiety disorder, obsessive-compulsive disorder), Substance abuse (alcohol or sedative-hypnotic withdrawal).
Pharmacologically induced
Anticonvulsants, Central adrenergic blockers, Diuretics, Selective serotonin reuptake inhibitors, Steroids, Stimulants
Clssification of insomnia:
a- Tranient
b- Short term
c- Long term
a- transient:
usually is situational, caused by environmental changes or life stresses, e.g. travelling, hospitalization, participation in an important or stressful event. Transient insomnia is self limiting and lassts for less than a week, if more sever stresses are present, it may progress to short term insomnia.
b- Short term:
In more sever life stresses (e.g. death or bereavement of loss a job).It lasts 1-3 weeks and if not managed properly, it may progress to chronic insomnia.
c-chronic insomnia (long term):
it lasts for more than 3 weeks often it is results of a medical problem, psycholoic dysfunction (e.g. depression) or substance abuse.
Nonpharmacological treatment of insomnia:
In many cases insomnia can be treated without sedative-hypnotics. Education about normal sleep and habits for good sleep hygiene are often sufficient interventions. Nonpharmacologic interventions for insomnia frequently consist of short-term cognitive behavioral therapies, most commonly stimulus control therapy, sleep restriction,
relaxation therapy, cognitive therapy, paradoxical intention, and education on good sleep hygiene (recommendation for insomnia below, part1 and part 2). In patients age 55 and older, a recent study indicates that cognitive behavioral therapy may be more effective than pharmacologic therapy at improving certain measures of insomnia.
Nonpharmacologic Recommendations for Insomnia
Parts 1:
Stimulus control procedures:
1- Establish regular time to wake up and to go to sleep ( including weekends).
2- Sleep only as much as necessary to feel rested.
3- Go to bed only when sleepy. Avoid long period of wakefulness in bed. Use the bed only for sleep or intimacy; do not read or watch television in bed.
4- Avoid trying to force sleep; if you do not fall asleep within 20-30 minutes, leave the bed and perform a relaxing activity(e.g. read, listen to music, or watch televsion) until drowsy. Repeat this as often as necessary.
5- Avoid daytime nap.
6- Schedule worry time during the day. Do not take your troubles to bed.
Part 2: Sleep hygiene recommendations:
1- Exercise routinely (3-4 times weekly), but not close to bedtime becuse this may cause arousal.
2- Create a comfortable sleep environment by avoiding temperature extremes, loud noises, and illuminated clocks in the bedroom.
3- Discontinue or reduce the use of alcohole, caffeine, and nicotine.
4- Avoid drinking larg quantities of liquids in the evening to prevent nighttime trips to the restroom.
5- Do something relaxing and enjoyable befor bedtime.
Humans typically have 4 to 6 cycles of Nonrapid eye movment (NREM) and rapid eye movment (REM) sleep each cycles lasting 70 to 120 minutes usually there is progression through four stages of NREM sleep which are befor first REM period.
The stages of NREM are:
Stage 1: transitional state which is the stage between wakefulness and sleep
Stage 2: 50% of sleep time is spent in these stage , sleep here is light sleep
Stage 3 & 4: deep sleep (delta sleep i.e., slow-wave sleep)
These stages categorized using sleep EEG
After the four stages then comes the REM period (rapid eye movment): these period neither light nor deep sleep it is chractrized by the body being more physiologically active than during other sleep stages while skeletal muscles are actively inhibted.the first REM period lasts 5-7 minutes, the sleep cycles repeats every 90-120 minutes, with each progressive REM period becoming longer and the time in deep sleep becoming shorter.
Insomnia :
defention of insomnia: in insomnia patients complain of difficulty falling asleep, difficulty maintaining a sleep (nocturnal awakening), not feelling rested in spite of a sufficient opportunity to sleep ( poor quality of sleep), or early morning awakening.
causes of insomnia:
Situational
Work or financial stress, major life events, interpersonal conflicts Jet lag or shift work.
Medical
Cardiovascular (angina, arrhythmias, heart failure), Respiratory (asthma, sleep apnea), Chronic pain, Endocrine disorders (diabetes, hyperthyroidism), GI (gastroesophageal reflux disease, ulcers), Neurologic (delirium, epilepsy, Parkinson’s disease), Pregnancy
Psychiatric
Mood disorders (depression, mania), Anxiety disorders (e.g., generalized anxiety disorder, obsessive-compulsive disorder), Substance abuse (alcohol or sedative-hypnotic withdrawal).
Pharmacologically induced
Anticonvulsants, Central adrenergic blockers, Diuretics, Selective serotonin reuptake inhibitors, Steroids, Stimulants
Clssification of insomnia:
a- Tranient
b- Short term
c- Long term
a- transient:
usually is situational, caused by environmental changes or life stresses, e.g. travelling, hospitalization, participation in an important or stressful event. Transient insomnia is self limiting and lassts for less than a week, if more sever stresses are present, it may progress to short term insomnia.
b- Short term:
In more sever life stresses (e.g. death or bereavement of loss a job).It lasts 1-3 weeks and if not managed properly, it may progress to chronic insomnia.
c-chronic insomnia (long term):
it lasts for more than 3 weeks often it is results of a medical problem, psycholoic dysfunction (e.g. depression) or substance abuse.
Nonpharmacological treatment of insomnia:
In many cases insomnia can be treated without sedative-hypnotics. Education about normal sleep and habits for good sleep hygiene are often sufficient interventions. Nonpharmacologic interventions for insomnia frequently consist of short-term cognitive behavioral therapies, most commonly stimulus control therapy, sleep restriction,
relaxation therapy, cognitive therapy, paradoxical intention, and education on good sleep hygiene (recommendation for insomnia below, part1 and part 2). In patients age 55 and older, a recent study indicates that cognitive behavioral therapy may be more effective than pharmacologic therapy at improving certain measures of insomnia.
Nonpharmacologic Recommendations for Insomnia
Parts 1:
Stimulus control procedures:
1- Establish regular time to wake up and to go to sleep ( including weekends).
2- Sleep only as much as necessary to feel rested.
3- Go to bed only when sleepy. Avoid long period of wakefulness in bed. Use the bed only for sleep or intimacy; do not read or watch television in bed.
4- Avoid trying to force sleep; if you do not fall asleep within 20-30 minutes, leave the bed and perform a relaxing activity(e.g. read, listen to music, or watch televsion) until drowsy. Repeat this as often as necessary.
5- Avoid daytime nap.
6- Schedule worry time during the day. Do not take your troubles to bed.
Part 2: Sleep hygiene recommendations:
1- Exercise routinely (3-4 times weekly), but not close to bedtime becuse this may cause arousal.
2- Create a comfortable sleep environment by avoiding temperature extremes, loud noises, and illuminated clocks in the bedroom.
3- Discontinue or reduce the use of alcohole, caffeine, and nicotine.
4- Avoid drinking larg quantities of liquids in the evening to prevent nighttime trips to the restroom.
5- Do something relaxing and enjoyable befor bedtime.
Pharmacological treatment
Pharmacological treatment of insomnia
Primary insomnia usually begins in early or middle adulthood and is rare in childhood or adolescence. More than 50% of the population complains of insomnia in their lifetime.
Despite the prevalence of insomnia, only 5% of individuals seek medical attention for management of their insomnia. Approximately 10% to 20% use nonprescription drugs or alcohol to selftreat. Of the 3% of the population who are prescribed sedative–hypnotics for insomnia, 11% report use exceeding 1 year.
Medication used in the treatment of insomnia:
1-OTC Agents:
Antihistamines exhibit sedating properties and are included in many over-the-counter sleep agents. They are effective in the treatment of mild (tansient and short term) insomnia and are generally safe. Diphenhydramine (25-50mg at bed time) and doxylamine are more sedating than pyrilamine. Increasing the dose of antihistamines will not produce a linear increase in response but will increase side effects. The safety and efficacy of antihistamines over placebo have been documented in several studies. Antihistamines are considered to be less effective than benzodiazepines, and have the disadvantages of anticholinergic side effects, which are especially troublesome in the elderly.
Ramelteon is a melatonin receptor agonist that has recently been approved for the treatment of sleep onset insomnia. Ramelteon is selective for the MT1 and MT2 melatonin receptors that are thought to regulate the circadian rhythm and sleep onset. The recommended dose is 8 mg taken at bedtime to induce sleep and although generally
well-tolerated, the most common adverse events reported are headache, dizziness, and somnolence. Ramelteon is not a controlled substance and can be a viable option for patients with a history of substance abuse. The over-the-counter supplement melatonin is a popular treatment for insomnia. Although melatonin has demonstrated efficacy
for inducing sleep, its use for the treatment of insomnia is not well-supported by clinical studies.
Valerian is an herbal sleep remedy that has been studied for its sedative-hypnotic properties in patients with insomnia. The mechanism of action is not fully understood but may involve increasing concentrations of γ-aminobutyric acid (GABA). The recommended dose for insomnia ranges from 300 to 600 mg. An equivalent dose
of dried herbal valerian root is 2 to 3 g soaked in 1 cup of hot water for 20 to 25 minutes.
2-Antidepressants:
Antidepressants are alternatives for patients with nonrestorative sleep who should not receive benzodiazepines, especially those who have depression, pain, or a risk of substance abuse. Using antidepressants for insomnia without depression is common but not well studied. Sedating antidepressants such as amitriptyline, doxepin, and nortriptyline are effective for inducing sleep continuity, although daytime sedation and side effects can be significant. Anticholinergic activity, adrenergic blockage, and cardiac conduction prolongation can be problematic, especially in the elderly and in overdose situations. Some of the new generation of antidepressants such as mirtazapine and nefazodone are also sedating. Mirtazapine can cause daytime sedation and weight gain.
Trazodone in doses of 25 to 100 mg at bedtime is sedating and can improve sleep continuity. Trazodone is popular for the treatment of insomnia in patients prone to substance abuse, as dependence is not a problem. Trazodone is frequently used in patients with selective serotonin reuptake inhibitor (SSRI) and bupropion induced
insomnia. Caution should be used to avoid serotonin syndrome when used in these combinations. Other side effects include carryover sedation and α-adrenergic blockade. Orthostasis can occur at any age, but it is more dangerous in the elderly. Priapism is a rare but serious side effect.
Benzodiazepine Receptor Agonists
The most commonly used treatments for insomnia have been the benzodiazepine receptor agonists. All benzodiazepine receptor agonists are effective as sedative-hypnotics, and are Food and Drug Administration (FDA) labeled for the treatment of insomnia as (Estazolam (ProSom), Eszopiclone (Lunesta), Flurazepam (Dalmane), Quazepam (Doral), Temazepam (Restoril), Triazolam (Halcion), Zaleplon (Sonata), Zolpidem (Ambien)). The benzodiazepine receptor agonists consist of the newer nonbenzodiazepine GABAA agonists and the traditional benzodiazepines. All benzodiazepine receptor agonists bind to GABAA receptors in the brain resulting in stimulatory effects on GABAergic transmission and hyperpolarization of neuronal membranes. Traditional benzodiazepines have sedative, anxiolytic, muscle relaxant,
and anticonvulsant properties; newer nonbenzodiazepine GABA agonists possess only sedative properties.
Benzodiazepine Hypnotics
Benzodiazepines relieve insomnia by reducing sleep latency and increasing total sleep time. Benzodiazepines increase stage 2 sleep while decreasing REM, stage 3, and stage 4 sleep. Benzodiazepines are very safe, and fatal overdoses are rare unless they are taken in
combination with central nervous system (CNS) depressants or alcohol. Benzodiazepine hypnotics should not be prescribed for individuals with sleep apnea, a history of substance abuse, or during pregnancy. Patients should be instructed to avoid alcohol and other CNS depressants.
Pharmacokinetics The choice of a particular benzodiazepine can be based on its pharmacokinetic profile. When used as a single dose, the extent of distribution and elimination half-life is important in predicting the duration of action. However, after multiple doses, the elimination half-life and formation of active metabolites determine the extent of drug accumulation and resultant clinical effects. Elderly patients, liver dysfunction, and drug interactions can prolong drug effects. The pharmacokinetic profiles of benzodiazepine receptor agonists are summarized in Table 1.
TABLE 1: Pharmacokinetics of Benzodiazepine Receptor Agonists
Generic Name (Brand Name) tmax (hours) Daily Dose Range (mg)
Estazolam (ProSom) 2 1-2
Eszopiclone (Lunesta) 1-1.5 2-3
Flurazepam (Dalmane) 1 15-30
Quazepam (Doral) 2 7.5-15
Temazepam (Restoril) 1.5 15-30
Triazolam (Halcion) 1 0.125-0.25
Zaleplon (Sonata) 1 5-10
Zolpidem (Ambien) 1.6 5-10
Adverse Effects: Side effects are dose dependent and vary according to the pharmacokinetics of the individual benzodiazepine. High doses with long or intermediate elimination half-lives have a greater potential for producing daytime sedation and performance impairment. These effects include excessive drowsiness, psychomotor incoordination, decreased concentration, and cognitive deficits. Tolerance to benzodiazepine hypnotic effects develops sooner with triazolam (after 2 weeks of continuous use) than with other benzodiazepine hypnotics. Most traditional benzodiazepines maintain hypnotic efficacy for 1 month. However, tolerance can develop with time. Rapidly eliminated benzodiazepines have less potential for daytime sedation. Anterograde amnesia, an impairment of memory and recall of events occurring after the dose is taken, has been reported with most benzodiazepine receptor agonists. Rebound insomnia is characterized by increased wakefulness beyond baseline amounts that last for one to two nights after abrupt discontinuation of benzodiazepine receptor agonists. Rebound insomnia occurs more frequently after high doses of triazolam, even when ingested intermittently. The lowest effective dosage should be used to minimize rebound insomnia and avoid adverse effects on memory. Benzodiazepine half-lives are prolonged in older patients, increasing the potential for drug accumulation and the incidence of CNS side effects. Prolonged sedation and cognitive and psychomotor impairment are concerns in the elderly. Benzodiazepine receptor agonists with long elimination half-lives are generally not first-line agents. There is an association between falls and hip fractures and the use of benzodiazepines with long elimination half-lives; thus flurazepam and quazepam should be avoided in elderly patients.
Primary insomnia usually begins in early or middle adulthood and is rare in childhood or adolescence. More than 50% of the population complains of insomnia in their lifetime.
Despite the prevalence of insomnia, only 5% of individuals seek medical attention for management of their insomnia. Approximately 10% to 20% use nonprescription drugs or alcohol to selftreat. Of the 3% of the population who are prescribed sedative–hypnotics for insomnia, 11% report use exceeding 1 year.
Medication used in the treatment of insomnia:
1-OTC Agents:
Antihistamines exhibit sedating properties and are included in many over-the-counter sleep agents. They are effective in the treatment of mild (tansient and short term) insomnia and are generally safe. Diphenhydramine (25-50mg at bed time) and doxylamine are more sedating than pyrilamine. Increasing the dose of antihistamines will not produce a linear increase in response but will increase side effects. The safety and efficacy of antihistamines over placebo have been documented in several studies. Antihistamines are considered to be less effective than benzodiazepines, and have the disadvantages of anticholinergic side effects, which are especially troublesome in the elderly.
Ramelteon is a melatonin receptor agonist that has recently been approved for the treatment of sleep onset insomnia. Ramelteon is selective for the MT1 and MT2 melatonin receptors that are thought to regulate the circadian rhythm and sleep onset. The recommended dose is 8 mg taken at bedtime to induce sleep and although generally
well-tolerated, the most common adverse events reported are headache, dizziness, and somnolence. Ramelteon is not a controlled substance and can be a viable option for patients with a history of substance abuse. The over-the-counter supplement melatonin is a popular treatment for insomnia. Although melatonin has demonstrated efficacy
for inducing sleep, its use for the treatment of insomnia is not well-supported by clinical studies.
Valerian is an herbal sleep remedy that has been studied for its sedative-hypnotic properties in patients with insomnia. The mechanism of action is not fully understood but may involve increasing concentrations of γ-aminobutyric acid (GABA). The recommended dose for insomnia ranges from 300 to 600 mg. An equivalent dose
of dried herbal valerian root is 2 to 3 g soaked in 1 cup of hot water for 20 to 25 minutes.
2-Antidepressants:
Antidepressants are alternatives for patients with nonrestorative sleep who should not receive benzodiazepines, especially those who have depression, pain, or a risk of substance abuse. Using antidepressants for insomnia without depression is common but not well studied. Sedating antidepressants such as amitriptyline, doxepin, and nortriptyline are effective for inducing sleep continuity, although daytime sedation and side effects can be significant. Anticholinergic activity, adrenergic blockage, and cardiac conduction prolongation can be problematic, especially in the elderly and in overdose situations. Some of the new generation of antidepressants such as mirtazapine and nefazodone are also sedating. Mirtazapine can cause daytime sedation and weight gain.
Trazodone in doses of 25 to 100 mg at bedtime is sedating and can improve sleep continuity. Trazodone is popular for the treatment of insomnia in patients prone to substance abuse, as dependence is not a problem. Trazodone is frequently used in patients with selective serotonin reuptake inhibitor (SSRI) and bupropion induced
insomnia. Caution should be used to avoid serotonin syndrome when used in these combinations. Other side effects include carryover sedation and α-adrenergic blockade. Orthostasis can occur at any age, but it is more dangerous in the elderly. Priapism is a rare but serious side effect.
Benzodiazepine Receptor Agonists
The most commonly used treatments for insomnia have been the benzodiazepine receptor agonists. All benzodiazepine receptor agonists are effective as sedative-hypnotics, and are Food and Drug Administration (FDA) labeled for the treatment of insomnia as (Estazolam (ProSom), Eszopiclone (Lunesta), Flurazepam (Dalmane), Quazepam (Doral), Temazepam (Restoril), Triazolam (Halcion), Zaleplon (Sonata), Zolpidem (Ambien)). The benzodiazepine receptor agonists consist of the newer nonbenzodiazepine GABAA agonists and the traditional benzodiazepines. All benzodiazepine receptor agonists bind to GABAA receptors in the brain resulting in stimulatory effects on GABAergic transmission and hyperpolarization of neuronal membranes. Traditional benzodiazepines have sedative, anxiolytic, muscle relaxant,
and anticonvulsant properties; newer nonbenzodiazepine GABA agonists possess only sedative properties.
Benzodiazepine Hypnotics
Benzodiazepines relieve insomnia by reducing sleep latency and increasing total sleep time. Benzodiazepines increase stage 2 sleep while decreasing REM, stage 3, and stage 4 sleep. Benzodiazepines are very safe, and fatal overdoses are rare unless they are taken in
combination with central nervous system (CNS) depressants or alcohol. Benzodiazepine hypnotics should not be prescribed for individuals with sleep apnea, a history of substance abuse, or during pregnancy. Patients should be instructed to avoid alcohol and other CNS depressants.
Pharmacokinetics The choice of a particular benzodiazepine can be based on its pharmacokinetic profile. When used as a single dose, the extent of distribution and elimination half-life is important in predicting the duration of action. However, after multiple doses, the elimination half-life and formation of active metabolites determine the extent of drug accumulation and resultant clinical effects. Elderly patients, liver dysfunction, and drug interactions can prolong drug effects. The pharmacokinetic profiles of benzodiazepine receptor agonists are summarized in Table 1.
TABLE 1: Pharmacokinetics of Benzodiazepine Receptor Agonists
Generic Name (Brand Name) tmax (hours) Daily Dose Range (mg)
Estazolam (ProSom) 2 1-2
Eszopiclone (Lunesta) 1-1.5 2-3
Flurazepam (Dalmane) 1 15-30
Quazepam (Doral) 2 7.5-15
Temazepam (Restoril) 1.5 15-30
Triazolam (Halcion) 1 0.125-0.25
Zaleplon (Sonata) 1 5-10
Zolpidem (Ambien) 1.6 5-10
Adverse Effects: Side effects are dose dependent and vary according to the pharmacokinetics of the individual benzodiazepine. High doses with long or intermediate elimination half-lives have a greater potential for producing daytime sedation and performance impairment. These effects include excessive drowsiness, psychomotor incoordination, decreased concentration, and cognitive deficits. Tolerance to benzodiazepine hypnotic effects develops sooner with triazolam (after 2 weeks of continuous use) than with other benzodiazepine hypnotics. Most traditional benzodiazepines maintain hypnotic efficacy for 1 month. However, tolerance can develop with time. Rapidly eliminated benzodiazepines have less potential for daytime sedation. Anterograde amnesia, an impairment of memory and recall of events occurring after the dose is taken, has been reported with most benzodiazepine receptor agonists. Rebound insomnia is characterized by increased wakefulness beyond baseline amounts that last for one to two nights after abrupt discontinuation of benzodiazepine receptor agonists. Rebound insomnia occurs more frequently after high doses of triazolam, even when ingested intermittently. The lowest effective dosage should be used to minimize rebound insomnia and avoid adverse effects on memory. Benzodiazepine half-lives are prolonged in older patients, increasing the potential for drug accumulation and the incidence of CNS side effects. Prolonged sedation and cognitive and psychomotor impairment are concerns in the elderly. Benzodiazepine receptor agonists with long elimination half-lives are generally not first-line agents. There is an association between falls and hip fractures and the use of benzodiazepines with long elimination half-lives; thus flurazepam and quazepam should be avoided in elderly patients.
Diarrhea
Diarrhea
Diarrhea is an increased frequency and decreased consistency of fecal discharge as compared with an individual’s normal bowel pattern. Frequency and consistency are variable within and between individuals. For example, some individuals defecate as many as three times a day, while others defecate only two or three times per week.
Acute Diarrhea
More than 90% of cases of acute diarrhea are caused by infectious agents; these cases are often accompanied by vomiting, fever, and abdominal pain. The remaining 10% or so are caused by medications, toxic ingestions, ischemia, and other conditions.
Infectious Agents
Most infectious diarrheas are acquired by fecal-oral transmission or, more commonly, via ingestion of food or water contaminated with pathogens from human or animal feces. In the immunocompetent person, the resident fecal microflora, containing >500 taxonomically distinct species, are rarely the source of diarrhea and may actually play a role in suppressing the growth of ingested pathogens. Disturbances of flora by antibiotics can lead to diarrhea by reducing the digestive function or by allowing the overgrowth of pathogens, such as Clostridium difficile. Acute infection or injury occurs when the ingested agent overwhelms the host's mucosal immune and nonimmune (gastric acid, digestive enzymes, mucus secretion, peristalsis, and suppressive resident flora) defenses. Established clinical associations with specific enteropathogens may offer diagnostic clues.
In the United States, five high-risk groups are recognized:
1. Travelers. Nearly 40% of tourists to endemic regions of Latin America, Africa, and Asia develop so-called traveler's diarrhea, most commonly due to enterotoxigenic or enteroaggregative Escherichia coli as well as to Campylobacter, Shigella, Aeromonas, norovirus, Coronavirus and Salmonella. Visitors to Russia (especially St. Petersburg) may have increased risk of Giardia-associated diarrhea; visitors to Nepal may acquire Cyclospora. Campers, backpackers, and swimmers in wilderness areas may become infected with Giardia. Cruise ships may be affected by outbreaks of gastroenteritis caused by agents such as Norwalk virus.
2. Consumers of certain foods. Diarrhea closely following food consumption at a picnic, banquet, or restaurant may suggest infection with Salmonella, Campylobacter, or Shigella from chicken; enterohemorrhagic E. coli (O157:H7) from undercooked hamburger; Bacillus cereus from fried rice; Staphylococcus aureus or Salmonella from mayonnaise or creams; Salmonella from eggs; and Vibrio species, Salmonella, or acute hepatitis A from seafood, especially if raw.
3. Immunodeficient persons. Individuals at risk for diarrhea include those with either primary immunodeficiency (e.g., IgA deficiency, common variable hypogammaglobulinemia, chronic granulomatous disease) or the much more common secondary immunodeficiency states (e.g., AIDS, senescence, pharmacologic suppression). Common enteric pathogens often cause a more severe and protracted diarrheal illness, and, particularly in persons with AIDS, opportunistic infections, such as by Mycobacterium species, certain viruses (cytomegalovirus, adenovirus, and herpes simplex), and protozoa (Cryptosporidium, Isospora belli, Microsporida, and Blastocystis hominis) may also play a role. In patients with AIDS, agents transmitted venereally per rectum (e.g., Neisseria gonorrhoeae, Treponema pallidum, Chlamydia) may contribute to proctocolitis. Persons with hemochromatosis are especially prone to invasive, even fatal, enteric infections with Vibrio species and Yersinia infections and should avoid raw fish.
4. Daycare attendees and their family members. Infections with Shigella, Giardia, Cryptosporidium, rotavirus, and other agents are very common and should be considered.
5. Institutionalized persons. Infectious diarrhea is one of the most frequent categories of nosocomial infections in many hospitals and long-term care facilities; the causes are a variety of microorganisms but most commonly C. difficile.
The pathophysiology underlying acute diarrhea by infectious agents produces specific clinical features that may also be helpful in diagnosis. Profuse watery diarrhea secondary to small bowel hypersecretion occurs with ingestion of preformed bacterial toxins, enterotoxin-producing bacteria, and enteroadherent pathogens. Diarrhea associated with marked vomiting and minimal or no fever may occur abruptly within a few hours after ingestion of the former two types; vomiting is usually less, and abdominal cramping or bloating is greater; fever is higher with the latter. Cytotoxin-producing and invasive microorganisms all cause high fever and abdominal pain. Invasive bacteria and Entamoeba histolytica often cause bloody diarrhea (referred to as dysentery). Yersinia invades the terminal ileal and proximal colon mucosa and may cause especially severe abdominal pain with tenderness mimicking acute appendicitis.
Finally, infectious diarrhea may be associated with systemic manifestations. Reiter's syndrome (arthritis, urethritis, and conjunctivitis) may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia. Yersiniosis may also lead to an autoimmune-type thyroiditis, pericarditis, and glomerulonephritis. Both enterohemorrhagic E. coli (O157:H7) and Shigella can lead to the hemolytic-uremic syndrome with an attendant high mortality rate. The syndrome of postinfectious IBS has now been recognized as a complication of infectious diarrhea. Acute diarrhea can also be a major symptom of several systemic infections including viral hepatitis, listeriosis, legionellosis, and toxic shock syndrome.
Table 1 Association between Pathobiology of Causative Agents and Clinical Features in Acute Infectious Diarrhea
Pathobiology/Agents Incubation Period Vomiting Abdominal Pain Fever Diarrhea
Toxin producers
Preformed toxin
Bacillus cereus, Staphylococcus aureus, 1–8 h 3–4+ 1–2+ 0–1+ 3–4+, watery
Clostridium perfringens 8–24 h
Enterotoxin
Vibrio cholerae, enterotoxigenic Escherichia coli, Klebsiella pneumoniae, Aeromonas species 8–72 h 2–4+ 1–2+ 0–1+ 3–4+, watery
Enteroadherent
Enteropathogenic and enteroadherent E. coli, Giardia organisms, cryptosporidiosis, helminths 1–8 d 0–1+ 1–3+ 0–2+ 1–2+, watery, mushy
Cytotoxin-producers
Clostridium difficile 1–3 d 0–1+ 3–4+ 1–2+ 1–3+, usually watery, occasionally bloody
Hemorrhagic E. coli 12–72 h 0–1+ 3–4+ 1–2+ 1–3+, initially watery, quickly bloody
Invasive organisms
Minimal inflammation
Rotavirus and Norwalk agent 1–3 d 1–3+ 2–3+ 3–4+ 1–3+, watery
Variable inflammation
Salmonella, Campylobacter, and Aeromonas species, Vibrio parahaemolyticus, Yersinia 12 h–11 d 0–3+ 2–4+ 3–4+ 1–4+, watery or bloody
Severe inflammation
Shigella species, enteroinvasive E. coli, Entamoeba histolytica 12 h–8 d 0–1+ 3–4+ 3–4+ 1–2+, bloody
Other Causes
Side effects from medications are probably the most common noninfectious cause of acute diarrhea, and etiology may be suggested by a temporal association between use and symptom onset. Although innumerable medications may produce diarrhea, some of the more frequently incriminated include antibiotics, cardiac antidysrhythmics, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs), certain antidepressants, chemotherapeutic agents, bronchodilators, antacids, and laxatives. Occlusive or nonocclusive ischemic colitis typically occurs in persons >50 years; often presents as acute lower abdominal pain preceding watery, then bloody diarrhea; and generally results in acute inflammatory changes in the sigmoid or left colon while sparing the rectum. Acute diarrhea may accompany colonic diverticulitis and graft-versus-host disease. Acute diarrhea, often associated with systemic compromise, can follow ingestion of toxins including organophosphate insecticides, amanita and other mushrooms, arsenic, and preformed environmental toxins in seafood, such as ciguatera and scombroid. Conditions causing chronic diarrhea can also be confused with acute diarrhea early in their course. This confusion may occur with inflammatory bowel disease (IBD) and some of the other inflammatory chronic diarrheas that may have an abrupt rather than insidious onset and exhibit features that mimic infection.
Diarrhea is an increased frequency and decreased consistency of fecal discharge as compared with an individual’s normal bowel pattern. Frequency and consistency are variable within and between individuals. For example, some individuals defecate as many as three times a day, while others defecate only two or three times per week.
Acute Diarrhea
More than 90% of cases of acute diarrhea are caused by infectious agents; these cases are often accompanied by vomiting, fever, and abdominal pain. The remaining 10% or so are caused by medications, toxic ingestions, ischemia, and other conditions.
Infectious Agents
Most infectious diarrheas are acquired by fecal-oral transmission or, more commonly, via ingestion of food or water contaminated with pathogens from human or animal feces. In the immunocompetent person, the resident fecal microflora, containing >500 taxonomically distinct species, are rarely the source of diarrhea and may actually play a role in suppressing the growth of ingested pathogens. Disturbances of flora by antibiotics can lead to diarrhea by reducing the digestive function or by allowing the overgrowth of pathogens, such as Clostridium difficile. Acute infection or injury occurs when the ingested agent overwhelms the host's mucosal immune and nonimmune (gastric acid, digestive enzymes, mucus secretion, peristalsis, and suppressive resident flora) defenses. Established clinical associations with specific enteropathogens may offer diagnostic clues.
In the United States, five high-risk groups are recognized:
1. Travelers. Nearly 40% of tourists to endemic regions of Latin America, Africa, and Asia develop so-called traveler's diarrhea, most commonly due to enterotoxigenic or enteroaggregative Escherichia coli as well as to Campylobacter, Shigella, Aeromonas, norovirus, Coronavirus and Salmonella. Visitors to Russia (especially St. Petersburg) may have increased risk of Giardia-associated diarrhea; visitors to Nepal may acquire Cyclospora. Campers, backpackers, and swimmers in wilderness areas may become infected with Giardia. Cruise ships may be affected by outbreaks of gastroenteritis caused by agents such as Norwalk virus.
2. Consumers of certain foods. Diarrhea closely following food consumption at a picnic, banquet, or restaurant may suggest infection with Salmonella, Campylobacter, or Shigella from chicken; enterohemorrhagic E. coli (O157:H7) from undercooked hamburger; Bacillus cereus from fried rice; Staphylococcus aureus or Salmonella from mayonnaise or creams; Salmonella from eggs; and Vibrio species, Salmonella, or acute hepatitis A from seafood, especially if raw.
3. Immunodeficient persons. Individuals at risk for diarrhea include those with either primary immunodeficiency (e.g., IgA deficiency, common variable hypogammaglobulinemia, chronic granulomatous disease) or the much more common secondary immunodeficiency states (e.g., AIDS, senescence, pharmacologic suppression). Common enteric pathogens often cause a more severe and protracted diarrheal illness, and, particularly in persons with AIDS, opportunistic infections, such as by Mycobacterium species, certain viruses (cytomegalovirus, adenovirus, and herpes simplex), and protozoa (Cryptosporidium, Isospora belli, Microsporida, and Blastocystis hominis) may also play a role. In patients with AIDS, agents transmitted venereally per rectum (e.g., Neisseria gonorrhoeae, Treponema pallidum, Chlamydia) may contribute to proctocolitis. Persons with hemochromatosis are especially prone to invasive, even fatal, enteric infections with Vibrio species and Yersinia infections and should avoid raw fish.
4. Daycare attendees and their family members. Infections with Shigella, Giardia, Cryptosporidium, rotavirus, and other agents are very common and should be considered.
5. Institutionalized persons. Infectious diarrhea is one of the most frequent categories of nosocomial infections in many hospitals and long-term care facilities; the causes are a variety of microorganisms but most commonly C. difficile.
The pathophysiology underlying acute diarrhea by infectious agents produces specific clinical features that may also be helpful in diagnosis. Profuse watery diarrhea secondary to small bowel hypersecretion occurs with ingestion of preformed bacterial toxins, enterotoxin-producing bacteria, and enteroadherent pathogens. Diarrhea associated with marked vomiting and minimal or no fever may occur abruptly within a few hours after ingestion of the former two types; vomiting is usually less, and abdominal cramping or bloating is greater; fever is higher with the latter. Cytotoxin-producing and invasive microorganisms all cause high fever and abdominal pain. Invasive bacteria and Entamoeba histolytica often cause bloody diarrhea (referred to as dysentery). Yersinia invades the terminal ileal and proximal colon mucosa and may cause especially severe abdominal pain with tenderness mimicking acute appendicitis.
Finally, infectious diarrhea may be associated with systemic manifestations. Reiter's syndrome (arthritis, urethritis, and conjunctivitis) may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia. Yersiniosis may also lead to an autoimmune-type thyroiditis, pericarditis, and glomerulonephritis. Both enterohemorrhagic E. coli (O157:H7) and Shigella can lead to the hemolytic-uremic syndrome with an attendant high mortality rate. The syndrome of postinfectious IBS has now been recognized as a complication of infectious diarrhea. Acute diarrhea can also be a major symptom of several systemic infections including viral hepatitis, listeriosis, legionellosis, and toxic shock syndrome.
Table 1 Association between Pathobiology of Causative Agents and Clinical Features in Acute Infectious Diarrhea
Pathobiology/Agents Incubation Period Vomiting Abdominal Pain Fever Diarrhea
Toxin producers
Preformed toxin
Bacillus cereus, Staphylococcus aureus, 1–8 h 3–4+ 1–2+ 0–1+ 3–4+, watery
Clostridium perfringens 8–24 h
Enterotoxin
Vibrio cholerae, enterotoxigenic Escherichia coli, Klebsiella pneumoniae, Aeromonas species 8–72 h 2–4+ 1–2+ 0–1+ 3–4+, watery
Enteroadherent
Enteropathogenic and enteroadherent E. coli, Giardia organisms, cryptosporidiosis, helminths 1–8 d 0–1+ 1–3+ 0–2+ 1–2+, watery, mushy
Cytotoxin-producers
Clostridium difficile 1–3 d 0–1+ 3–4+ 1–2+ 1–3+, usually watery, occasionally bloody
Hemorrhagic E. coli 12–72 h 0–1+ 3–4+ 1–2+ 1–3+, initially watery, quickly bloody
Invasive organisms
Minimal inflammation
Rotavirus and Norwalk agent 1–3 d 1–3+ 2–3+ 3–4+ 1–3+, watery
Variable inflammation
Salmonella, Campylobacter, and Aeromonas species, Vibrio parahaemolyticus, Yersinia 12 h–11 d 0–3+ 2–4+ 3–4+ 1–4+, watery or bloody
Severe inflammation
Shigella species, enteroinvasive E. coli, Entamoeba histolytica 12 h–8 d 0–1+ 3–4+ 3–4+ 1–2+, bloody
Other Causes
Side effects from medications are probably the most common noninfectious cause of acute diarrhea, and etiology may be suggested by a temporal association between use and symptom onset. Although innumerable medications may produce diarrhea, some of the more frequently incriminated include antibiotics, cardiac antidysrhythmics, antihypertensives, nonsteroidal anti-inflammatory drugs (NSAIDs), certain antidepressants, chemotherapeutic agents, bronchodilators, antacids, and laxatives. Occlusive or nonocclusive ischemic colitis typically occurs in persons >50 years; often presents as acute lower abdominal pain preceding watery, then bloody diarrhea; and generally results in acute inflammatory changes in the sigmoid or left colon while sparing the rectum. Acute diarrhea may accompany colonic diverticulitis and graft-versus-host disease. Acute diarrhea, often associated with systemic compromise, can follow ingestion of toxins including organophosphate insecticides, amanita and other mushrooms, arsenic, and preformed environmental toxins in seafood, such as ciguatera and scombroid. Conditions causing chronic diarrhea can also be confused with acute diarrhea early in their course. This confusion may occur with inflammatory bowel disease (IBD) and some of the other inflammatory chronic diarrheas that may have an abrupt rather than insidious onset and exhibit features that mimic infection.
Subscribe to:
Posts (Atom)