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

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

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

9. Oxidation/ conjugation
metabulism
Oxidation/ conjugation

10. 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

11. 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.

13. 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

14. 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

15. Extrapyramidal reactions have been associated with the use of midazolam

16. 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.

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

21. کدام بنزودیازپین بدون نسخه است

22. 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.

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

24. 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

25. 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.

26. Activated charcoal conservative
TREATMENT
Activated charcoal
conservative

27. 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

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

30. 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

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

32. 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

33. 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

34. مصرف بنزودیازپین در بارداریd

35. مصرف بنزودیازپین در شیردهی

36. 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

37. از توجه شما سپاسگزارم

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

40. 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

41. MEPROBAMATE

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

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

45. 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.

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

47. 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