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Hyperventilation syndrome
Hyperventilation syndrome• Hyperventilation syndrome (HVS) represents a relatively
common emergency department (ED) presentation that is readily recognized by most clinicians.
• The underlying patho-physiology has not been clearly elucidated.
• HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms.
• Inducing a drop in PaCO2 through voluntary
hyperventilation reproduces these symptoms. • Many patients with HVS do not manifest low
PaCO2 during attacks.
Hyperventilation syndrome• A better term for this syndrome might be behavioral
breathlessness or psychogenic dyspnea, with hyperventilation seen as a consequence rather than a cause of the condition.
• Some patients may be physiologically at risk for the development of psychogenic dyspnea.
• Symptoms of HVS and panic disorder overlap considerably, though the 2 conditions remain distinct.
• Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as a symptom, whereas only 25% of patients with HVS manifest panic disorder.
The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies the anxiety disorders into the following categories:
• Substance-induced anxiety disorder• Generalized anxiety disorder• Panic disorder• Acute stress disorder• Posttraumatic stress disorder (PTSD)• Adjustment disorder with anxious features• Obsessive-compulsive disorder (OCD)• Social phobia• Specific phobia and agoraphobia
Hyperpnea or hyperventilation• Hyperpnea or hyperpnoea is increased depth of breathing when
required to meet metabolic demand of body tissues, such as during or following exercise, or when the body lacks oxygen (hypoxia), for instance in high altitude or as a result of anemia.
• Tachypnea differs from hyperpnea in that tachypnea is rapid shallow breaths, while hyperpnea is deep breaths.
• In hyperpnoea, the increased breathing rate is desirable as it meets the metabolic needs of the body.
• In hyperventilation, the rate of ventilation is inappropriate for the body's needs (except in respiratory acidosis, when CO2 needs to be breathed off). The resulting decrease in CO2 concentration results in the typical symptoms of light-headedness, tingling in peripheries, visual disturbances etc. In hyperpnoea, there are generally no such symptoms .
Panic Disorder • Panic disorder is characterized by the
spontaneous and unexpected occurrence of panic attacks, the frequency of which can vary from several attacks per day to only a few attacks per year.
• Panic attacks can occur in other anxiety disorders but occur without discernible predictable precipitant in panic disorder
• To make the diagnosis of panic disorder, panic attacks cannot directly or physiologically result from substance use, medical conditions, or another psychiatric disorders
Panic attacks are a period of intense fear in which 4 of 13 defined symptoms develop abruptly and peak rapidly less than 10 minutes from symptom onset.
• Palpitations • Sweating• Trembling or shaking• Sense of shortness of breath or smothering• Feeling of choking• Chest pain or discomfort• Nausea or abdominal distress• Feeling dizzy, unsteady, light-headed, or faint• Derealization or depersonalization (feeling detached from oneself)• Fear of losing control or going crazy• Fear of dying• Numbness or tingling sensations• Chills or hot flashes
• Agoraphobia is defined as anxiety toward places or situations in which escape may be difficult or embarrassing
• Most cases of agoraphobia develop as a complication of panic disorders.
• A person previously experiences a panic attack in a specific situation or environment and this triggers a vicious circle.
• They begin to worry so much about having a panic attack again that they feel the symptoms of panic attack returning when they are in a similar situation or environment. This then causes the person to avoid that particular situation or environment.
Conversion disorder, factitious disorder, and malingering
• Conversion disorder, factitious disorder, and malingering have one major characteristic in common: they represent conditions that are not ‘real’.
• Properly diagnosing your patient with one of these psychiatric ailments will allow you to create appropriate plans of care for your patients .
1. Conversion Disorder: is a psychiatric condition that results in a neurological complaint or symptom, without any underlying neurological cause.
• Patient’s may experience seizures (i.e. ‘pseudo-seizures’), weakness, non-responsiveness, numbness, and even vision loss.
• The symptoms are not intentional, yet upon further investigation no biological explanation for the symptoms can be found.
• The name “conversion disorder” formerly known as "hysteria", comes from Sigmund Freud who stated that stress can cause a psychiatric ailment to ‘convert’ to a medical problem.
• It is thought that symptoms arise in response to stressful situations affecting a patient's mental health.
2. Factitious Disorder (Munchausen Syndrome )
• Factitious Disorder (a Somatoform Disorder): is a condition where patients intentionally fake disease, or intentionally cause disease in order to play the ‘patient role’.
• The main distinction between this and conversion disorder is the intentional nature of factitious disorder.
• Often referred to a factitious disorder is characterized by patients frequently feigning illness to obtain attention, sympathy, or other emotional feedback.
• They achieve this goal through exaggerating symptoms, deliberately faking symptoms, or even intentionally creating real symptoms.
3. Malingering• Malingering is the intentional faking or creating of
illness in order to obtain secondary gain (e.g. workers compensation, disability payments, avoiding work or jail time, pain medication, etc.).
• Malingering is NOT a psychiatric illness; this is the first major distinction from the other two disorders.
• Malingering is an intentional abuse of the medical system to obtain personal benefit.
• Malingerers abuse the system to obtain secondary gain while patients with factitious disorder attempt only to obtain emotional, or primary gain. In simpler terms, the end goal of a malingerer usually involves monetary value, while the goals of patients with factitious disorder have no such value
QUICK REVIEW• Conversion Disorder: Unintentional,
due to emotional stressors, no ‘gain’ to the patient
• Factitious Disorder (Munchausen): Intentional, primary or ‘emotional’ gain
• Malingering: Intentional, secondary and often monetary gain.
Pathophysiology of HVS
• Acute HVS accounts for only 1% of cases but is more easily diagnosed.
• Chronic HVS can present with a myriad of respiratory, cardiac, neurologic, or gastrointestinal (GI) symptoms without any clinically apparent over-breathing by the patient.
• Because of the subtlety of hyperventilation, many patients with chronic HVS are admitted and undergo extensive and expensive testing in an attempt to discover organic causes of their complaints.
• Certain stressors provoke an exaggerated respiratory response, including emotional distress, sodium lactate, caffeine, isoproterenol, cholecystokinin, and Co2 .
Pathophysiology
• Patients with HVS tend to breathe by using the upper thorax rather than the diaphragm, and this results in chronic over-inflation of the lungs.
• When stress induces a need to take a deep breath, the deep breathing is perceived as dyspnea.
• The sensation of dyspnea creates anxiety, which encourages more deep breathing, and a vicious circle is created.
Etiology• Proprioceptors in the lung and chest wall signal the
brain with a “suffocation alarm” that triggers release of excitatory neurotransmitters that are responsible for many of the symptoms such as palpitations, tremor, anxiety, and diaphoresis.
• The incidence of HVS is higher in first-degree relatives than in the general population, but no clear genetic factors have been identified.
Epidemiology• As many as 10% of patients in a general internal
medicine practice are reported to have HVS as their primary diagnosis.
• The peak incidence is between the ages of 15 and 55 years, but cases have been reported in all age groups except infants.
• HVS has a strong female preponderance: the female-to-male ratio may be as high as 7:1.
Prognosis• Patients with chronic HVS experience multiple
exacerbations throughout their lives.• Children who experience acute HVS often continue this
pattern into adulthood. • Many patients have associated disorders (eg,
agoraphobia) that may dominate the clinical picture.
• Patients who are treated with breathing retraining, stress reduction therapy, and various medications (eg, benzodiazepines or selective serotonin reuptake inhibitors [SSRIs]) experience significant reductions in the frequency and the severity of exacerbations.
• Death attributable to HVS is extremely rare.
Prognosis• A leftward shift in the oxyhemoglobin dissociation curve
and vasospasm related to low PaCO2 could cause myocardial ischemia in patients with coronary artery disease (CAD) and hyperventilation syndrome.
• Certain patients are disabled psychologically by their symptoms, and many patients carry false diagnoses.
• Patients with HVS often undergo unnecessary testing and suffer from the complications of these interventions (eg, angiography, thrombolytics, or nasal reconstruction).
• Withholding such therapy may be difficult in a patient with crushing chest pain and dyspnea. the chronicity of the condition often causes different physicians to repeat these unnecessary investigations.
Patient Education
• Patients should receive :
1- Clear explanation of the underlying patho-physiology and
2- should be instructed in the technique of deflation of the upper chest followed by controlled diaphragmatic breathing.
Complications• The complications encountered in patients with
this syndrome are related mainly to the invasive procedures and investigations (eg, angiography) that are used in the workup of HVS .
• Complications may also occur as a result of symptoms produced indirectly by hyperventilation (eg, injuries sustained in a fall during a syncopale episode attributable to hyperventilation).
Screening for OSA prior to surgery• Pulse oximetry as a single metric of sleep apnea lacks the
sensitivity and specificity of PSG and multi-channel home sleep testing.
• If the goal is only to cipher out those with an AHI of 15 or 20 or more, pulse oximetry can be considered.
• Centers for Medicare and Medicaid Services, 2009 reported that the final decision supporting equally effective testing utilizing PSG and home sleep tests, as measured by outcomes and patient compliance.
• While patients with mild OSA may not require preoperative PAP therapy, patients with moderate and severe OSA who have been on PAP therapy should continue treatment in the preoperative period .
• Patients who have been noncompliant with instructions for CPAP use prior to surgery and are in need of CPAP postsurgery, pose the highest risk of potential complications.
Acute hyperventilation
• Patients often present dramatically, with agitation, hyperpnea and tachypnea, dyspnea, wheezing, chest pain , dizziness, palpitations, tetanic cramps (eg, carpopedal spasm), paresthesias, generalized weakness, and Syncope. The patient often complains of a sense of suffocation.
• An emotionally stressful precipitating event can often be identified.
• Wheezing may be heard because of broncho-spasm from hypo-carbia.
Carpopedal spasm occurs when acute hypocarbia causes reduced ionized calcium and phosphate levels, resulting in involuntary contraction of the feet or (more commonly) the hands .
Cardiac symptoms• The chest pain associated with HVS usually has atypical
features, but on occasion, it may closely resemble typical angina.
• It tends to last hours rather than minutes, and is often relieved rather than provoked by exercise. It is usually unrelieved by nitroglycerin.
• The diagnosis of HVS should be considered in young patients without cardiac risk factors who present with chest pain, particularly if the pain is associated with paresthesias and carpo-pedal spasm.
• ECG abnormalities may include prolonged QT interval, ST depression or elevation, and T-wave inversion.
Cardiac symptoms• In patients with subcritical coronary artery
stenosis, the vasospasm induced by hypocarbia may be sufficient to provoke myocardial injury.
• The incidence of HVS is high among patients with mitral valve prolapse (MVP), and the chest pain associated with MVP may be due to hyperventilation.
• Prinzmetal angina (ie, coronary artery vasospasm) is triggered by HVS, but the chest pain associated with this syndrome normally would be expected to respond to nitrates or calcium channel blockers.
Central nervous system symptoms• Central nervous system (CNS) symptoms occur because
hypocapnia causes reduced cerebral blood flow (CBF).CBF decreases by 2% for every 1 mm Hg decrease in PaCO2.
• Symptoms of dizziness, weakness, confusion, and agitation are common . Patients may experience visual hallucinations, syncope or seizure .
• Paresthesias occur more commonly in the upper extremity and are usually bilateral. Perioral numbness is very common.
Gastrointestinal symptoms• (eg, bloating, belching, flatus, or epigastric pressure)
may result from aerophagia.
Metabolic changes• Acute metabolic changes result from intracellular shifts and
increased protein binding of various electrolytes during respiratory alkalosis.
• Acute secondary hypocalcemia can result in carpopedal spasm, muscle twitching, a prolonged QT interval, and positive Chvostek and Trousseau signs.
• Hypokalemia tends to be less pronounced than hypocalcemia but can produce generalized weakness.
• Acute secondary hypophosphatemia is common and may contribute to paresthesias and generalized weakness.
Chvostek’s sign is twitching of facial muscles in response to tapping over the area of the facial nerve Trousseau’s sign is carpopedal spasm that results from ischemia, such as that induced by pressure applied to the upper arm from an inflated sphygmomanometer cuff .
• Chvostek’s sign is neither sensitive nor specific for hypocalcemia, since it is absent in about one third of patients with hypocalcemia and is present in approximately 10% of persons with normal calcium levels.
• Trousseau’s sign is more sensitive and specific; it is present in 94% of patients with hypo-calcemia and in only 1% of persons with normal calcium levels.
Chronic hyperventilation• The diagnosis of chronic HVS is much more difficult than
that of acute HVS because hyperventilation is usually not clinically apparent. Often, these patients have already undergone extensive medical investigations and have been assigned several misleading diagnoses.
• Two thirds of patients with chronic HVS have a persistently slightly low PaCO2 with compensatory renal excretion of bicarbonate, resulting in a near-normal pH level.
• These patients tend to have more prominent CNS symptoms than patients who maintain normal PaCO2 during attacks.
• Usually present with dyspnea and chest pain. • Frequent sighing respirations (2-3 breaths/min) and
frequent yawning are noted.
Chronic hyperventilation• The respiratory alkalosis can be maintained with
occasional deep sighing respirations, which are observed often in patients with chronic HVS.
• When faced with an additional stress that provokes hyperventilation, the physiologic acid-base reserve is less, and these patients become symptomatic more readily than patients without HVS.
• Dry mouth occurs with mouth breathing and anxiety.
• Many of these patients suffer from obsessive-compulsive disorders, experience sexual and marital difficulties, and have poor adaptations to stress.
• Chronic HVS may have symptoms that mimic those of virtually any serious organic disorder, but they usually have atypical features of these diseases.
Differential Diagnoses :• Asthma • Atrial Fibrillation• Myocardial Infarction• Diabetic Ketoacidosis• Metabolic Acidosis• Nasopharyngeal Stenosis• Pneumothorax, Pneumomediastinum• Pulmonary Embolism• Respiratory Distress Syndrome, Adult• Carbon monoxide poisoning• Panic Disorders
TAKE THE TEST WITH THE NIJMEGEN QUESTIONNAIRE
A score of over 23 out of 64 suggests a positive diagnosis of
over breathing / hyperventilation syndrome.
Never=Never Rarely=Once a month Sometimes = Once a week (maybe a little more)
Often=More than once a week but not daily Very often=daily or more
Never 0
Rarely 1
Sometime
2
Often 3
Very Often 4
Chest
pain
Feeling tense
Blurred vision
Dizzy spells
Feeling confused
Faster or deeper breathing Short of breath
Tight feelings in chest
Bloated feeling in stomach tingling fingers
Unable to breathe deeply
Stiff fingers or arms Tight feelings round mouth
Cold hands or feet Palpitations
Feeling of anxiety
Approach Considerations• Upon a first attack of acute HVS, the diagnosis depends
on recognizing the typical constellation of signs and symptoms and ruling out the serious conditions that can cause the presenting symptoms.
• Acute coronary syndrome (ACS) and pulmonary embolism (PE) are the 2 most common serious entities that may present similarly to HVS.
• Clinical assessment is sufficient to rule these out. More specific testing is sometimes warranted.
• A standard workup for atypical chest pain, including pulse oximetry, chest radiography, and ECG, may still be warranted depending on the clinical picture.
Approach Considerations• Patients with a history of HVS who have undergone an
appropriate workup at some earlier time may not need any further laboratory evaluation in the setting of a recurrence. Recognition of the typical constellation of dyspnea, agitation, dizziness, atypical chest pain, tachypnea and hyperpnea, paresthesias, and carpopedal spasm in a young, otherwise healthy patient with an adequate prior evaluation is sufficient to make the diagnosis.
• A low pulse oximetry reading in a patient who is hyperventilating should never be attributed to HVS. The patient should always be evaluated for other causes of hyperventilation.
Approach Considerations
• A normal pulse oximetry reading is not helpful, because a severe defect in gas exchange can easily be masked by hyperventilation.
• A fraction of patients with chronic PE will have compensated chronic hyperventilation that may mimic primary chronic hyperventilation.
• ABG is indicated if any doubt exists as to the patient’s underlying respiratory status; it may be helpful when HVS-induced acidosis is suspected, or when shunting or impaired pulmonary gas exchange is considered.
Approach Considerations• ABG sampling confirms a compensated
respiratory alkalosis in a majority of cases. The pH is typically near normal, with a low PaCO2 and a low bicarbonate level.
• ABG sampling is also useful in ruling out toxicity from carbon monoxide poisoning, which may present similarly to HVS.
• Toxicology screening is indicated. • If acute PE is being considered, ELISA D-dimer
assay may be helpful.
Approach Considerations• Imaging studies are not indicated when the
diagnosis of HVS is clear. • Because PE can present with findings identical
to those of HVS, a first-ever episode of acute HVS may warrant V/Q scanning or CT pulmonary angiography to rule out perfusion defects.
• Chest radiography is indicated for patients who are at high risk for cardiac or pulmonary pathology.
Approach Considerations• ECG changes are common and may include the
following:
1- ST depression or elevation
2- Prolonged QT interval
3- T-wave inversion
4- Sinus tachycardia• Rebreathing into a paper bag is not recommended in
the field. Deaths have occurred in patients with acute myocardial infarction (MI), pneumothorax, and pulmonary embolism (PE) who were initially misdiagnosed with HVS and treated with paper bag rebreathing.
Rebreathing into a paper bag
1- Have the hyperventilating person breathe slowly into a paper bag that's held closely around his or her mouth and nose. 2- The person should breathe like this for five to seven minutes. 3-Talk to the individual the entire time. Try to distract him or her and make the person feel comfortable and safe. 4- If symptoms fail to improve or the person loses consciousness, take him or her to the emergency room.
Breathing Techniques• Rebreathing into a paper bag is no longer a
recommended technique, because significant hypoxia and death have been reported.
• Paper bag rebreathing is often unsuccessful in reversing the symptoms of HVS, because patients have difficulty complying with the technique. Moreover, carbon dioxide itself may be a chemical trigger for anxiety in these patients.
• Simple reassurance and an explanation of how hyperventilation produces the patient’s symptoms are usually sufficient to terminate the episode.
• Provoking the symptoms by having the patient voluntarily hyperventilate for 3-4 minutes often convinces the patient of the diagnosis.
Breathing Techniques
• Most patients with HVS tend to breathe with the upper thorax and have hyper-inflated lungs throughout the respiratory cycle. Because residual lung volume is high, they are unable to achieve full tidal volume and experience dyspnea.
• Physically compressing the upper thorax and having patients exhale maximally decreases hyperinflation of the lungs.
• Instructing patients to breathe abdominally, using the diaphragm more than the chest wall, often leads to improvement in subjective dyspnea and eventually corrects many of the associated symptoms.
What is “calm breathing”?• Calm breathing (sometimes called “diaphragmatic
breathing”) is a technique that helps you slow down your breathing when feeling stressed or anxious.
• Newborn babies naturally breathe this way, and singers, wind instrument players, and yoga practitioners use this type of breathing.
• Diaphragmatic breathing slows the respiratory rate, gives patients a distracting maneuver to perform when attacks occur, and provides patients with a sense of self-control during episodes of hyperventilation.
• This technique has been shown to be very effective in a high proportion of patients with HVS.
How to Do It? • Calm breathing involves taking smooth,
slow, and regular breaths.• Sitting upright is usually better than
lying down or slouching, because it can increase the capacity of your lungs to fill with air.
• It is best to 'take the weight' off your shoulders by supporting your arms on the side-arms of a chair, or on your lap.
How to Do It ?1. Take a slow breath in through the nose, breathing into
your lower belly (for about 4 seconds)
2. Hold your breath for 1 or 2 seconds
3. Exhale slowly through the mouth (for about 4 seconds)
4. Wait a few seconds before taking another breath• About 6-8 breathing cycles per minute is often helpful to
decrease anxiety, but find your own comfortable breathing rhythm.
• These cycles regulate the amount of oxygen you take in so that you do not experience the fainting, tingling, and giddy sensations that are sometimes associated with overbreathing.
Hyperventilation syndrome and asthma
• Hyperventilation syndrome is a common and often disabling condition. Traditional treatment consists of reassurance and anxiolytic drugs. Hyperventilation is known to precipitate an asthmatic reaction. A retrospective review of patients with hyperventilation syndrome was performed to ascertain the frequency of asthma as well as the response to bronchodilator medication. Forty-seven patients were seen. Thirty-eight were tested, and asthma was proved in 36. Two additional patients had positive clinical responses with bronchodilators. Thus, asthma was identified in 38 of 47 consecutive patients seen for hyperventilation syndrome (80 percent), and asthma was proved in 36 of 38 of patients tested (95 percent). Hyperventilation syndrome was eliminated in 29 of 35 patients (90 percent) treated with a combination of explanation and bronchodilator treatment.
Hyperventilation syndrome and asthma • Several studies have shown that patients with asthma
have significantly higher anxiety scores than normal and are more likely to have clinically diagnosed panic disorder., patients with panic disorders, hyperventilation, or “overbreathing” may have unidentified airways reversibility.4 investigated 47 patients referred for hyperventilation syndrome using methacholine challenge and reversibility testing and judged 38 of them to have asthma.5 The hyperventilation symptoms were eliminated in 29 with a combination of explanation and bronchodilators.
Pharmacologic Therapy• Several medications, including benzodiazepines and
selective serotonin reuptake inhibitors (SSRIs), have been employed to reduce the frequency and severity of episodes of hyperventilation.
• These agents require prolonged use and are best managed by a consultant on an ongoing outpatient basis rather than through sporadic prescriptions after an ED visit.
• Use of benzodiazepines for stress relief and for resetting the trigger for hyperventilation is effective, but again, patients may require prolonged treatment.
Pharmacologic Therapy• Benzodiazepines are useful in the treatment of
hyperventilation resulting from anxiety and panic attacks.
• By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and to facilitate inhibitory GABA neurotransmission and the actions of other inhibitory transmitters.
• Alprazolam (xanax) is indicated for treatment of anxiety and management of panic attacks.
• Lorazepam (ativan) is a sedative-hypnotic of the benzodiazepine class that has a short time to onset of effect and a relatively long half-life.
Anxiolytic AGENT– Benzodiazepines
– Serotonergic antidepressants– Mebicar– Selank
– Bromantane
– Emoxypine
– Azapirones– Barbiturates– Hydroxyzine– Pregabalin
– ALCOHOl
– Beta blockers
XANAX
• Xanax, the trade name of a drug called “alprazolam,” is a benzodiazepine medication that is prescribed by doctors for short-term management of anxiety or sleep disorders. Xanax produces its calming effects by suppressing the inhibitory receptors in the brain and central nervous system to decrease the abnormal excitement in the brain that leads to anxiety symptoms. While most individuals who take Xanax follow the doctor’s instructions, taking the drug at the proper time at the proper dose and discontinuing usage as indicated. Unfortunately for some, Xanax can become addicting if taken in large quantities over a long period of time.
Statistics
• Xanax addiction has been a growing problem for many individuals in the past few years. While the exact statistics for these medications are not as well known, there has been research done on the benzodiazepine class of medication. In 2011, it is estimated that about 61,000 people sought treatment for benzodiazepine abuse. The rates have only been rising in the past couple of years.
Dependence And Withdrawal Reactions OF XANAX
• Certain adverse clinical events, some life-threatening, are a direct consequence of physical dependence to XANAX. These include a spectrum of withdrawal symptoms; the most important is seizure . Even after relatively shortterm use at the doses recommended for the treatment of transient anxiety and anxiety disorder ( 0.75 to 4.0 mg per day), there is some risk of dependence. Spontaneous reporting system data suggest that the risk of dependence and its severity appear to be greater in patients treated with doses greater than 4 mg/day and for long periods (more than 12 weeks). However, in a controlled postmarketing discontinuation study of panic disorder patients, the duration of treatment (3 months compared to 6 months) had no effect on the ability of patients to taper to zero dose. In contrast, patients treated with doses of XANAX greater than 4 mg/day had more difficulty tapering to zero dose than those treated with less than 4 mg/day.
Signs and Symptoms OF XANAX addiction
Mood symptoms • Depression• Anxiety• Mood swings• Hyperactivity
• Rage• Agitation• Mania• Restlessness
Signs and Symptoms OF XANAX addiction• Behavioral symptoms:• “Doctor shopping,” or visiting a number of doctors to obtain more prescriptions for
Xanax• Stealing or borrowing Xanax• Forging prescriptions• Risky behaviors• Decreased inhibitions• Hostility and violence• Neglecting family or personal responsibilities• Declining occupational or school performance• Changes in appetite• Taking higher doses than what was prescribed• Chewing pills to make them work faster• Crushing and snorting pills to increase effects• Taking more tablets more frequently than prescribed
Signs and Symptoms OF XANAX addicted • Physical symptoms:• Decreased urination• Swelling in hands and feet• Coordination difficulties• Dry mouth• Stuffy nose• Sweating• Constipation• Diarrhea• Fluctuations in weight
• Dizziness
Signs and Symptoms OF XANAX addicted
• Blurred or double vision• Slurred speech• Headaches• Drowsiness• Heart palpitations• Jaundice• Tachycardia• Tremors Seizures
BENZODIAZEPINE during pregnancy• Benzodiazepines can potentially cause fetal harm when administered
to pregnant women. If XANAX is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Because of experience with other members of the benzodiazepine class, XANAX is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. Because use of these drugs is rarely a matter of urgency, their use during the first trimester should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution advised of therapy should be considered. Patients should be that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.
Drugs Demonstrated To Be Cyp 3A Inhibitors On The Basis Of Clinical Studies Involving Alprazolam (Caution And Consideration Of Appropriate Alprazolam Dose Reduction Are Recommended During Coadministration With The Following Drugs
• Nefazodone—Coadministration of nefazodone increased alprazolam concentration two-fold.
• Fluvoxamine—Coadministration of fluvoxamine approximately doubled the maximum plasma concentration of alprazolam, decreased clearance by 49%, increased half-life by 71%, and decreased measured psychomotor performance.
• Cimetidine—Coadministration of cimetidine increased the maximum plasma concentration of alprazolam by 86%, decreased clearance by 42%, and increased half-life by 16%.
Drugs Demonstrated To Be Cyp 3A Inhibitors On The Basis Of Clinical Studies Involving Alprazolam (Caution And Consideration Of Appropriate Alprazolam Dose Reduction Are Recommended During Coadministration With The Following Drugs
• HIV protease inhibitors – Interactions involving HIV protease inhibitors (eg, ritonavir) and alprazolam are complex and time dependent. Low doses of ritonavir resulted in a large impairment of alprazolam clearance, prolonged its elimination half-life and enhanced clinical effects. However, upon extended exposure to ritonavir, CYP3A induction offset this inhibition. This interaction will require a dose-adjustment or discontinuation of alprazolam
Selective Serotonin Uptake Blockers (SSRI)• e.g. Fluoxetine; Fluvoxamine; Paroxetine;
Sertraline; Citalopram (see table 3).• Pharmacological Activities:
MOA : Selective uptake of 5-HT in the presynaptic cleft.
Why they are better choice as compared to TCA?
Table 3: Effect of SSRIs on Reuptake
5-HT reuptake5-HT reuptake Noradrenaline Noradrenaline reuptakereuptake
5-HT2 5-HT2 antagonistsantagonists
Selective serotonin Selective serotonin reuptake inhibitorsreuptake inhibitors
CitalopramCitalopram
FluoxetineFluoxetine
FluvxamineFluvxamine
ParoxetineParoxetine
SertralineSertraline
++
++
++
++
++
--
--
--
--
--
--
--
--
--
--
Side Effects of SSRI • Almost have no cardiovascular manifestations as
compared to TCA.• Nausea and vomiting and decrease appetite How?
• Insomnia and anxiety (with Fluoxetine ; Citalopram; bu not with Paroxetine.
• Impotence and sexual dysfunction (in male and female)
• Decrease weight.
Drug Cardiotoxicty Nausea Anticholinergic SedationDrug Cardiotoxicty Nausea Anticholinergic Sedation
effectseffects
Citalopram Citalopram ? ++ _ _ ? ++ _ _
FluoxetineFluoxetine - ++ _ _ - ++ _ _
FluvoxamineFluvoxamine _ +++ _ + _ +++ _ +
Paroxetine Paroxetine _ ++ + + _ ++ + +
SertralineSertraline _ ++ _ _ _ ++ _ _
Table 4: Side effects of SSRIs
Table 2: Side Effects of Tricyclic antidepressants
Relative Side effectsRelative Side effects Reuptake inhibitionReuptake inhibition
SedatioSedationn
Cardio-Cardio-toxicitytoxicity
HypotensiHypotensionon
Anti-Anti-CholinnergiCholinnergicc
NENE
AmitriptylineAmitriptyline
AmoxapineAmoxapine
ClomipramineClomipramine
DesipramineDesipramine
DothiepinDothiepin
DoxepinDoxepin
ImipramineImipramine
LofepramineLofepramine
NortriptylineNortriptyline
ProtriptylineProtriptyline
TrimipramineTrimipramine
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0/+0/+
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+/-+/-
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+/-+/-
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Birth Defects & Pregnancy
• Many antidepressants, including SSRIs, can increase the risk of birth defects if taken while pregnant.
• Pregnant women suffering from depression face a difficult decision. They can risk potential harm to their babies by taking a class of antidepressants that are the current standard of treatment — or face other possible dangers to themselves and their babies if the disease is left untreated for months
Birth Defects & Pregnancy
• Doctors’ current antidepressant drugs of choice during pregnancy include Prozac and Zoloft. Both drugs belong to the family of drugs known as selective serotonin reuptake inhibitors (SSRIs). Drugs in this class have largely been assigned a “C” grade for safety during pregnancy by the U.S. Food and Drug Administration (FDA). That means they have been known to harm animals taking them in large doses, but because researchers cannot ethically test any drug on a human baby, the FDA states that effects on unborn humans remain unproven.
Birth Defects & Pregnancy
There is one SSRI that the FDA and its manufacturer warn women not to take during pregnancy — paroxetine (Paxil), which carries a grade D. Drugs that are labeled as D have been shown to be a risk to a human fetus.
• Researchers have consistently raised questions about the safety of SSRIs during pregnancy. And today, more and more studies are linking SSRIs to increased risks of serious birth defects when the drugs are taken during pregnancy
defects when the(SSRIs) are taken during pregnancy.
persistent pulmonary hypertention of newborn
cleft lip and palate,
respiratory distress at birth.
Autism
Anencephaly
Heart Defects
