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Showing posts with label CNS. Show all posts
Showing posts with label CNS. Show all posts
Classification of Anxiety Disorders
By Piscean | Saturday, March 10, 2012 | Posted in , | With 0 comments
Post-Traumatic Stress Disorder
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Post-Traumatic Stress Disorder
Post-traumatic stress disorder develops following a traumatic event that elicited an immediate reaction of fear, helplessness, or horror. It is more common in women than in men, and is the fourth most common psychiatric disorder. Traumatic events that involve interpersonal violence (e.g., assault, rape, or torture) are more likely to cause post-traumatic stress disorder than are traumatic events that do not (e.g., car accidents or natural disasters).
Social Anxiety Disorder
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Social Anxiety Disorder
Social anxiety disorder, formerly known as social phobia, is characterized by an intense, irrational fear of situations in which one might be scrutinized by others, or might do something that is embarrassing or humiliating. Exposure to the feared situation almost always elicits anxiety. As a result, the person avoids the situation, or, if it cannot be avoided, endures it with intense anxiety. Manifestations include blushing, stuttering, sweating, palpitations, dry throat, and muscle tension.

Social anxiety disorder is one of the most common psychiatric disorders and the most common anxiety disorder. Th is disorder typically begins during the teenage years, and if left untreated, is likely to continue lifelong.
Obsessive-Compulsive Disorder
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Obsessive-Compulsive Disorder
Obsessive-compulsive disorder is a potentially disabling condition characterized by persistent obsessions and compulsions that cause marked distress, consume at least one hour per day, and signifi cantly interfere with daily living. An obsession is defined as a recurrent, persistent thought, impulse, or mental image that is unwanted and distressing, and comes involuntarily to mind despite attempts to ignore or suppress it. A compulsion is a ritualized behavior or mental act that a person is driven to perform in response to his or her obsessions.
Panic Disorder
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Panic Disorder
Panic disorder is characterized by recurrent, intensely uncomfor table episodes known as panic attacks. Panic attacks have a sudden onset, reaching peak intensity within ten minutes. Symptoms may include trembling, shortness of breath, heart palpitations, chest pain (or chest tightness), sweating, nausea, dizziness (or slight vertigo), light-headedness, hyperventilation, paresthesias (tingling sensations), and sensations of choking or smothering. These symptoms typically disappear within 30 minutes. Many patients go to an emergency department because they think they are having a heart attack. Some patients experience panic attacks daily; others have only one or two per month. According to the American Journal of Psychiatry, the incidence of panic disorders in women is two to three times that seen in men. Onset of panic disorder usually occurs in the late teens or early twenties.
Generalized Anxiety Disorder
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Generalized Anxiety Disorder
Generalized anxiety disorder is a chronic condition characterized by uncontrollable worrying. Most patients with generalized anxiety disorder also have another psychiatric disorder, usually depression. The hallmark of this disorder is unrealistic or excessive anxiety about several events or activities (e.g., work or school performance). Generalized anxiety disorder may last for six months or longer.
Anxiety disorders
By Piscean | | Posted in , | With 0 comments

Anxiety disorders are common occurrences in society today. These disorders can prove stressful and disruptive to those suff ering from them. There are a variety of anxiety disorders for which drug therapy may be therapeutic. Antianxiety drugs or hypnotics are the most common classifi cations of medications that may be used to treat these disorders. Sleep disturbances are also extremely common. If continuous, they have the potential to seriously disrupt normal day-to-day living. Many people suff ering from a sleep disorder want to turn to drugs to solve their problem. Th e use of drugs in many of these situations is usually undesirable. Many of the medications discussed in this chapter are also administered as muscle relaxants, preanesthetic medications, anticonvulsants, and therapeutic aids in psychiatry.
Pharmacology of CNS Drugs
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Drugs affecting the central nervous system (CNS) were among the first to be discovered by primitive humans and are still the group most widely used pharmacologic agents. In addition to their use in therapy, many CNS-active drugs are used without a prescription increase his sense of well-being.
The mechanisms by which various drugs work in the CNS have not always been well understood. Over the past three decades, however, dramatic progress has been made in the methodology of the pharmacology of the CNS. It is now possible to study the action of a drug on individual cells and ion channels, even in single synapses. Information obtained from these studies is based on several major developments in studies of central nervous system.
First, it is clear that nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission. With very few agents such as general anesthetics and alcohol may have nonspecific actions on membranes (although these exceptions are not fully accepted), but even these are not associated with mediation of the actions result in demonstrable alterations in synaptic transmission.
Second, drugs are among the most important tools to study all aspects of the physiology of the CNS, the mechanism of seizures in the setting of long-term memory. As described below, agonists that mimic natural transmitters (and in many cases are more selective than the endogenous substances) and antagonists are extremely useful in such studies. Natural Toxins: Tools for Characterizing ion channels, describes some of these substances.
Third, unraveling the actions of drugs of known clinical effectiveness has led to some of the most fruitful hypotheses on the mechanisms of disease. For example, information on the action of antipsychotic drugs on dopamine receptors has provided the basis of assumptions regarding the pathophysiology of schizophrenia. Studies on the effects of a variety of agonists and antagonists of-aminobutyric acid (GABA) has led to new concepts in the pathophysiology of several diseases, including anxiety and epilepsy.
Division of Nervous System
By Piscean | Tuesday, January 17, 2012 | Posted in , , | With 0 comments
Division of Nervous System
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Muscle relaxants
By Piscean | Monday, January 9, 2012 | Posted in , , | With 0 comments


Muscle relaxants
In this topic:
Baclofen
Dantrolene
Diazepam
Quinine
Use in rheumatology
Muscle relaxants: diazepam
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Muscle relaxants: diazepam
Diazepam is commonly used, as short-term therapy, for its muscle relaxant properties.
Muscle relaxants: dantrolene
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Muscle relaxants: dantrolene
Dantrolene works by a direct action on skeletal muscles in which it reduces muscle tone by depressing calcium-mediated myofibril contractions. It has no effect on neural pathways and has fewer central adverse effects than baclofen and diazepam. Dantrolene and diazepam are equally effective in spasticity caused by various upper motor neurone disorders. However, diazepam causes more drowsiness and dantrolene causes more muscle weakness.
After oral administration, the plasma half-life is approximately 9 hours.
Most patients who experience a reduction in spasticity with dantrolene also have an increase in weakness. Therefore it is mainly useful in bed-bound patients who would not be troubled by a decrease in muscle power. Adverse effects are common and the long-term safety and efficacy of dantrolene has not been established. Serious adverse effects include hepatitis (probably idiosyncratic), seizures and pleural effusions with pericarditis. Baseline liver function tests should be performed before treatment, and periodically during therapy (eg 3-monthly). The most common adverse reaction is muscle weakness, which can result in slurred speech, drooling and enuresis. Other common adverse effects are drowsiness, dizziness, diarrhoea, nausea and fatigue; these are usually transient.
Muscle relaxants: baclofen
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Muscle relaxants: baclofen
Baclofen is an analogue of gamma-aminobutyric acid (GABA) and may exert its effect by stimulating the GABAB receptor subtype.
The bioavailability of oral baclofen is 70% to 80%. The plasma elimination half-life averages 3 to 4 hours. Approximately 70% of the dose is excreted unchanged in the urine, necessitating dose reduction in patients with renal impairment. Baclofen passes only slowly across the blood–brain barrier. After oral administration, baclofen concentrations attained in the cerebrospinal fluid are approximately 12% of that in the plasma.
Baclofen may also be administered by continuous intrathecal infusion for intractable spasticity. The intrathecal doses are about 100 times less than oral doses.
Baclofen can cause weakness, drowsiness, dizziness, fatigue, headache, insomnia, confusion, ataxia, and respiratory and cardiovascular depression. It should not be used where there is a history of peptic ulcer. Use with tricyclic antidepressants (TCAs) can cause increased muscle weakness. Baclofen can also cause urinary frequency, dysuria, constipation and nausea. It should be withdrawn slowly as abrupt cessation can result in agitation, delirium and, occasionally, convulsions. The dose should be reduced slowly over 2 weeks.
Skeletal muscle relaxants: use in rheumatological diseases
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Skeletal muscle relaxants: use in rheumatological diseases
Muscle relaxants are sometimes used as adjuvants in the treatment of acute low back pain. These drugs include benzodiazepines (eg diazepam) and nonbenzodiazepines (eg baclofen, orphenadrine). Both groups have been found to reduce pain when compared with placebo; however, they are associated with adverse effects including drowsiness, dizziness and nausea. Refer to Benzodiazepines and Baclofen for more information about these medications.
Benzodiazepines
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Benzodiazepines: use in pain management and palliative care
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Benzodiazepines: use in pain management and palliative care 
Introduction
Benzodiazepines have a limited role in pain management and should only be considered for short-term use. They are not recommended for use in nonmalignant persistent pain.
Flumazenil, a benzodiazepine antagonist, can be used in hospitalised patients to reverse the therapeutic effects of benzodiazepines, including anaesthesia and sedation. Flumazenil should be administered under the guidance of an anaesthetist or experienced physician.
Clonazepam
The principal advantage of clonazepam is its strong anxiolytic and antiepileptic effect, but it also has sedative and muscle relaxant actions. It may be useful in the treatment of myoclonus. It is a long-acting benzodiazepine with no active metabolites.
The drop formulation makes clonazepam easy to administer orally, but care must be taken to ensure the mouth is moist. The parenteral preparation has been used subcutaneously
Diazepam
Diazepam has strong anxiolytic, muscle relaxant and antiepileptic effects, and moderate sedative effects. Diazepam has a long half-life, and its active metabolites with even longer half-lives accumulate in the body over time.
Diazepam is not suitable for intramuscular use because of poor and erratic absorption, but it is absorbed well orally and rectally. To administer rectally, use the oral or injectable solution in a syringe attached to a short catheter, and introduce alongside a well-lubricated gloved finger that has been inserted into the rectum. [Note 1]
Midazolam
Midazolam, a water-soluble benzodiazepine, is indicated for minor procedures, seizures, or as a sedative in an emergency when sedation is acceptable to aid symptom relief (eg asphyxia, exsanguination, severe restlessness). It has a rapid onset of action—2 to 3 minutes if given intravenously or 5 to 10 minutes if given subcutaneously—and a relatively short duration of action—15 minutes to several hours. Midazolam can also be administered by the buccal and intranasal routes. It has a plasma half-life of 2 to 5 hours.
Care needs to be exercised if midazolam is given intravenously because it may cause transient apnoea and hypotension. One active metabolite relies on renal excretion and can accumulate in patients with renal impairment. Enhanced effects may result from drug interactions with diltiazem, erythromycin, itraconazole, ketoconazole and possibly fluconazole.
Lorazepam
Lorazepam has some antinauseant activity in addition to anxiolytic (eg it is useful in panic attacks) and amnesic properties. It may be used for anticipatory emesis (nausea and vomiting often beginning before the administration of chemotherapy) in patients with poor control of emesis during previous cycles of chemotherapy. Lorazepam is a medium-acting benzodiazepine.
Alprazolam
Alprazolam has been used in the treatment of anxiety and panic disorder. It is a short-acting benzodiazepine with a rapid onset of action.
Note 1: There is no rectal formulation of diazepam marketed in Australia. A formulation for rectal use is prepared in some hospital pharmacies and provided under specialist advice to parents and carers who have been trained in its use. See, for example, the Melbourne Royal Children's Hospital website.
Benzodiazepines: use in epilepsy
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Introduction
The antiepileptic action of benzodiazepines involves modulation of the GABAA receptor, which opens the chloride channel and hyperpolarises the cell, leading to postsynaptic inhibition. Benzodiazepines are the preferred option in patients presenting with active generalised convulsive status epilepticus since they rapidly terminate seizures.
Clonazepam
The sedative effect and the development of tolerance substantially reduce the usefulness of clonazepam in the chronic treatment of epilepsy. Apart from the treatment of status epilepticus, the therapeutic role of clonazepam is limited; it is used mostly for refractory myoclonic seizures.
Common adverse effects are drowsiness, ataxia, excess salivary and bronchial secretions, and behavioural and personality changes. Behavioural adverse effects are particularly common in children.
Diazepam
Although diazepam has a long elimination half-life, it redistributes out of the central nervous system rapidly. It therefore has a relatively short duration of action (only 20 to 30 minutes) against seizures when given acutely. While it is highly effective in stopping seizures, its short duration of action requires that a longer-acting antiepileptic drug (eg phenytoin) be given after status epilepticus ceases.
Intravenous diazepam usually stops seizures within a few minutes. Intravenous diazepam should be administered undiluted. If diazepam for injection is diluted with sodium chloride 0.9% before administration, a fine white precipitate may form. The safety of administration with such a solution is not established.
Intramuscular diazepam is not recommended because of its variable and relatively inefficient absorption. Rectally administered diazepam is effective in terminating seizures in high-risk situations. [Note 1]
Midazolam
Effective midazolam plasma concentrations can be obtained after intramuscular, buccal or intranasal administration making it a useful option when intravenous access is difficult. The effect of a single dose wears off quickly because of its short elimination half-life.
Care needs to be exercised if midazolam is given intravenously because it may cause transient apnoea and hypotension. An active metabolite relies on renal excretion and may accumulate in patients with renal impairment. Enhanced effects may result from drug interactions with diltiazem, erythromycin, itraconazole, ketoconazole and possibly fluconazole.
Note 1: There is no rectal formulation of diazepam marketed in Australia. A formulation for rectal use is prepared in some hospital pharmacies and provided under specialist advice to parents and carers who have been trained in its use. See, for example, the Melbourne Royal Children's Hospital website.
Benzodiazepines: use in dentistry
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Benzodiazepines: use in dentistry
Benzodiazepines are the most commonly prescribed anxiolytic and sedative drugs because of their efficiency and their relatively low incidence of adverse effects.
Diazepam is a widely used sedative. It is available in tablets and in liquid form. Diazepam is reliably absorbed from the gut, with its effect becoming apparent after about 30 minutes. The optimum clinical effect is reached after one hour. A single oral dose of 10 mg for adults can be given one hour before the dental appointment.
Drug interactions with anxiolytics and hypnotics (Table 8.14L)
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Drug interactions with anxiolytics and hypnotics (Table 8.14L)
Anxiolytics include benzodiazepines and buspirone. Hypnotics include benzodiazepines, zolpidem and zopiclone.
Drug
Rating [NB1]
Interaction
Recommended action
Analgesics, opioid (including tramadol)
2
Respiratory depression with benzodiazepines, especially if given parenterally.
Monitor for respiratory depression.
Antiretrovirals: ritonavir, saquinavir
3
Increase plasma concentration of alprazolam, buspirone and triazolam (CYP3A4 inhibition).
Monitor for adverse effects.
Consider use of an alternative anxiolytic or hypnotic, eg lorazepam, oxazepam or temazepam.
Azole antifungals: fluconazole, itraconazole, ketoconazole
2
May increase plasma concentrations of alprazolam, triazolam, buspirone, zolpidem and zopiclone (CYP3A4 inhibition).
Monitor for adverse effects. Use an alternative benzodiazepine or alternative antifungal drug, eg terbinafine.
Calcium channel blockers
3
Diltiazem and verapamil may increase plasma concentrations of buspirone and triazolam (CYP3A4 inhibition).
Monitor for adverse effects. Use an alternative calcium channel blocker or alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
Cimetidine
3
Increases plasma concentrations of alprazolam, diazepam, nitrazepam and triazolam (CYP3A4 inhibition).
Monitor for adverse effects. Use an alternative H2-receptor blocker or alternative benzodiazepine, eg lorazepam, oxazepam or temazepam.
Clarithromycin -
Disulfiram
3
Decreases diazepam metabolism.
Monitor for adverse effects. Use an alternative drug, eg alprazolam, oxazepam or lorazepam.
ECT
2
Benzodiazepines raise seizure threshold, which may impair the efficacy of the ECT.
Taper and cease benzodiazepines before ECT.
Erythromycin -
Esomeprazole -
Macrolide antibiotics: clarithromycin, erythromycin
2
Increase plasma concentrations of alprazolam, triazolam, buspirone, and zopiclone (CYP3A4 inhibition).
Monitor for adverse effects. Use an alternative antibiotic, eg roxithromycin, or alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
MAOIs, irreversible nonselective
3
Hypertension reported rarely with buspirone.
Monitor for increased blood pressure or use an alternative drug.
Nefazodone -
Omeprazole -
Proton pump inhibitors: esomeprazole, omeprazole
3
Decreased clearance of diazepam reported (possibly inhibition of CYP3A, CYP2C9 or CYP2C19).
Monitor for adverse effects of diazepam or use alternative benzodiazepine or alternative proton pump inhibitor, eg rabeprazole
Rifabutin, rifampicin
3
Increased buspirone, diazepam, nitrazepam, triazolam, zolpidem and zopiclone metabolism. Temazepam not affected.
Monitor for decreased effect of anxiolytic or hypnotic.
Ritonavir -
Saquinavir -
SSRIs and nefazodone
2
Nefazodone inhibits metabolism (CYP3A4) of alprazolam, triazolam and zopiclone. Fluoxetine and fluvoxamine increase plasma alprazolam and diazepam concentrations. Unlikely with paroxetine or sertraline.
Monitor for benzodiazepine adverse effects or use alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
3
Several reports of adverse effects with fluoxetine and buspirone.
Monitor for increased adverse effects such as worsening of psychiatric symptoms, serotonergic effects or seizure with buspirone and fluoxetine.
Tramadol -
NB1:
Rating 1 – Avoid combination; risk always outweighs benefit.
Rating 2 – Usually avoid combination; use combination only under special circumstances.
Rating 3 – Minimise risk; take action as necessary to reduce risk.

Benzodiazepines: class information
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Benzodiazepines: class information
Benzodiazepines are effective in relieving anxiety symptoms and can induce sleep if given in large enough doses. They are also used for their antiepileptic actions, including the reduction of myoclonus, and for their skeletal muscle relaxant and amnesic effects. Their main disadvantage is physical dependence and they can impair performance and affect judgment so that driving and other skilled tasks can be impaired.
Benzodiazepines act by potentiating the action of gamma-aminobutyric acid (GABA) at the GABAA receptor. Interaction with the benzodiazepine receptor results in neuronal inhibition and inhibitory effects on the central nervous system (CNS). Most differences between benzodiazepines are explicable in terms of different pharmacokinetic properties (see Table 8.5).
There is little basis for the use of more than one benzodiazepine concurrently in any patient.

Pharmacokinetics: Benzodiazepines are generally rapidly and fully absorbed after oral ingestion with peak plasma concentrations occurring from 0.5 to 2 hours after administration. There are some differences in absorption rate between the various drugs. They are metabolised both by oxidation which may produce active compounds, and by glucuronidation which inactivates them. They differ widely in their rate of removal from the body.
Adverse effects, interactions and precautions: Drowsiness is a common initial reaction. Psychomotor performance may be impaired as may some memory functions. Older persons are particularly vulnerable to the adverse effects of ataxia (with consequent falls and injury), confusion, memory loss and cognitive impairment. In younger patients, ataxia, nystagmus, muscle weakness and dysarthria are reported less often. Dry mouth and blurred vision are sometimes troublesome. They can precipitate delirium. The potential for the development of tolerance to some actions, dependence and a withdrawal syndrome are important considerations. Dependence develops rarely in patients taking normal therapeutic doses of these drugs for short periods (eg 1 to 2 weeks). However, about a third of patients who have had long-term treatment may have difficulty in reducing or stopping benzodiazepines
Tolerance, a process of neuroadaptation, occurs more with the sedative and hypnotic effects than with other benzodiazepine actions. The degree of tolerance differs between patients. There is little evidence for the development of tolerance to the anxiolytic effects of benzodiazepines within 6 to 12 months. Even when tolerance develops it is uncommon for patients to increase the dose.
Patients with a history of dependence on alcohol and other drugs are more likely to become dependent or intentionally misuse benzodiazepines. All benzodiazepines can produce symptoms when the drug is withdrawn; these symptoms can be physical and psychological and are related to dose and duration of use. Abrupt discontinuation can result in symptoms of increasing anxiety, sleep disorder, aching limbs, nervousness and nausea. These are promptly relieved by reinstituting any benzodiazepine. Abrupt discontinuation in patients taking high doses, eg greater than 50 mg diazepam daily or equivalent, may be accompanied by seizures. Benzodiazepines should be avoided in patients with myasthenia gravis or severe respiratory impairment.
There are additive effects with alcohol and other CNS depressants (eg opioids). Many interactions with other drugs have been reported but are of dubious clinical significance (see Table 8.14L).