فلوشیپ سم شناسی بالینی عضو هیئت علمی دانشکده پزشکی دکتر سید خسرو قاسم پوری فلوشیپ سم شناسی بالینی عضو هیئت علمی دانشکده پزشکی

sedative, hypnotic, anxiolytic, amnestic, anticonvulsant, Benzodiazepines sedative, hypnotic, anxiolytic, amnestic, anticonvulsant, and muscle relaxant

PHARMACOLOGY benzodiazepines augment GABA’S inhibitory effect by increasing the frequency of channel openings

Oxidation/ conjugation metabulism Oxidation/ conjugation

All benzodiazepines are metabolized by the liver Some are just metabolized by different pathways that are less dependent on global liver function. The ‘LOT’ drugs are those metabolized mostly by conjugation. L – Lorazepam O – Oxazepam T – Temazepam The rest of the benzodiazepines are primarily metabolized via hepatic CYP-mediated oxidation. These may have prolonged duration of effect in patients with marked liver impairment, particularly the drugs with active metabolites such as diazepam, clonazepam, and midazolam

Most benzodiazepines are highly protein bound and lipophilic Most benzodiazepines are highly protein bound and lipophilic. They passively diffuse into the CNS, their main site of action. Because of their lipophilicity, benzodiazepines are extensively metabolized via oxidation and conjugation in the liver prior to their renal elimination.

nausea, vomiting, chest pain, joint pain, diarrhea, and incontinence Paradoxical reactions, including excitement, anxiety, aggression, hostile behavior, rage, and delirium, have been reported but are quite uncommon. Paradoxical reactions may occur more with hyperactive children and in psychiatric patients other effects that have been reported and that have unclear etiologies include headache, nausea, vomiting, chest pain, joint pain, diarrhea, and incontinence

These reactions are reported to occur from several minutes to 210 minutes after initiation of sedation. management strategies include administering higher doses of the benzodiazepines, adding other drugs such as opioids, stopping the procedure, and using flumazenil

Extrapyramidal reactions have been associated with the use of midazolam

Isolated benzodiazepine overdose has low mortality, and death is rare Isolated overdose with high-potency short-acting agents, such as alprazolam, temazepam,and triazolam, is associated with higher incidences of intensive careunit admissions, coma, and mechanical ventilation with toxicity compared to other benzodiazepines, such as diazepam.

The serum half life is not a good indicator of the duration of action in an acute ingestion

کدام بنزودیازپین بدون نسخه است

CLINICAL FEATURES the predominant manifestations of benzodiazepines are neurologic and are characterized by somnolence, dizziness, slurred speech confusion, ataxia, incoordination, and general impairment of intellectual function.

In the elderly, infants and children, protein-deficient persons, and those with hepatic disease, the neurologic effects of benzodiazepines may be prolonged or enhanced

Chronic use of benzodiazepines during pregnancy can result in withdrawal syndrome in the infant after birth such as “floppy baby syndrome” (sedation, hypotonia, apnea, cyanosis, hypothermia) and neonatal withdrawal (restlessness, hypertonia, tremors). nearly all benzodiazepines enter breast milk, and therefore, caution should be exercised in patients taking benzodiazepines

DIAGNOSIS A urine benzodiazepine screen can usually detect a short- acting agent (e.G.,Lorazepam) up to 3 days and a long- acting agent (e.G., Diazepam) up to 30 days after ingestion.

Activated charcoal conservative TREATMENT Activated charcoal conservative

BENZODIAZEPINE ANTAGONIST The dose of Flumazenil is 0.2 milligram IV, which can be repeated every minute,Titrated according to response or to a total dose of 3 milligrams

Anticonvulsants such as phenobarbital or propofol are recommended for flumazenil-induced seizures

BENZODIAZEPINE ABUSE AND WITHDRAWAL Reported withdrawal manifestations include anxiety, irritability, Insomnia, nausea, vomiting, tremor, sweating, and anorexia. Serious Manifestations, including confusion, disorientation, psychosis, and seizures, also have been reported

Withdrawal from highpotency benzodiazepines, such as alprazolam, may require higher doses of traditional benzodiazepines (e.G., IV diazepam) to achieve the appropriate clinical response

fractures, and motor vehicle accidents Those with hepatic dysfunction may have impaired metabolism,causing increased clinical effects Elderly patients taking benzodiazepines are at increased risk for falls, cognitive impairment, delirium, fractures, and motor vehicle accidents

Contraindications Because of their muscle relaxant action, benzodiazepines may cause respiratory depression in susceptible individuals. For that reason, they are contraindicated in people with myasthenia gravis, sleep apnea, bronchitis, and COPD , Pregnancy , Elderly

مصرف بنزودیازپین در بارداری d

مصرف بنزودیازپین در شیردهی

Withdrawal ● Sleep disturbance ● Irritability ● Anxiety, panic attacks ● Tremor ● Diaphoresis ● Poor concentration ● Nausea, vomiting ● Weight loss ● Palpitations ● Headache ● Muscle pain and stiffness More severe manifestations of benzodiazepine withdrawal may include seizures or psychotic symptoms

از توجه شما سپاسگزارم

Nonbenzodiazepine Sedatives Many nonbenzodiazepines were developed and are marketed For the treatment of insomnia

BUSPIRONE Buspirone is approved by the U.S. Food and drug administration for Treatment of anxiety disorders Because of its serotoninergic properties,Buspirone has been associated with serotonin syndrome

MEPROBAMATE

MELATONIN At therapeutic dosing, side effects from melatonin include fatigue, Headache, dizziness, and irritability

RAMELTEON Ramelteon is a highly selective agonist at the melatonin MT1 and MT2 Receptors, marketed for the treatment of insomnia

In overdose, sedation would be expected and treatment is supportive In overdose, sedation would be expected and treatment is supportive. ramelteon has not been associated with any potential for abuse and has minimal risk for producing withdrawal symptoms or rebound insomnia.

ZOLPIDEM, ZALEPLON, AND ZOPICLONE Zolpidem, zaleplon, and zopiclone are three nonbenzodiazepine sedative-hypnotics used to treat insomnia.

Zolpidem undergoes hepatic metabolism into three inactive metabolites, so dosage restrictions are recommended for those with hepatic impairment and those with chronic renal insufficiency. Common adverse effects include somnolence and nausea. Because of occasional psychomotor impairment, individuals should not drive or engage in hazardous activity the day following use of zolpidem. There are numerous reports of sleep walking or vivid dreams after its consumption. Following overdose, sedation (including coma) and vomiting can occur