Sleep inducing drugs

SLEEP INDUCING DRUGS

1. PRESENTED BY SUPREET MSC NURSING 2 ND YR SLEEP INDUCING DRUGS

2. The duration and pattern of sleep varies considerably among individuals. Age has an important effect on quantity and depth of sleep. It has been recognized that sleep is an architectured cyclic process. The different phases of sleep and their characteristics are— Sleep

3. From lying down to falling asleep and occasional nocturnal awakenings; constitutes 1–2% of sleep time. Eye movements are irregular or slowly rolling. Stage 0 (awake)

4. Eye movements are reduced but there may be bursts of rolling. Neck muscles relax. Occupies 3–6% of sleep time. Stage 1

5. (unequivocal sleep) θ waves with interspersed spindles, K complexes can be evoked on sensory stimulation; little eye movement; subjects are easily arousable . This comprises 40–50% of sleep time. Stage 3 (deep sleep transition) Eye movements are few; subjects are not easily arousable ; comprises 5–8% of sleep time. Stage 2

6. (cerebral sleep) δ activity predominates in EEG, K complexes cannot be evoked. Eyes are practically fixed , subjects are difficult to arouse. Night terror may occur at this time. It comprises 10–20% of sleep time. During stage 2, 3 and 4 heart rate, BP and respiration are steady and muscles are relaxed. Stages 3 and 4 together are called slow wave sleep (SWS). Stage 4

7. REM sleep (paradoxical sleep) EEG has waves of all frequency, K complexes cannot be elicited. There are marked, irregular and darting eye movements; dreams and nightmares occur, which may be recalled if the subject is aroused. Heart rate and BP fluctuate; respiration is irregular. Muscles are fully relaxed, but irregular body movements occur occasionally. STAGE 5

8. A drug that subdues excitement and calms the subject without inducing sleep, though drowsiness may be produced. Sedation refers to decreased responsiveness to any level of stimulation; is associated with some decrease in motor activity and ideation. Sedative

9. A drug that induces and/or maintains sleep, similar to normal arousable sleep. This is not to be confused with ‘hypnosis’ meaning a trans-like state in which the subject becomes passive and highly suggestible. Hypnotics

10. Barbiturates Long acting Short acting Ultra-short acting Phenobarbitone Butobarbitone Pentobarbitone Thiopentone Classification

11. Benzodiazepines Hypnotic Antianxiety Anticonvulsant Diazepam Flurazepam Nitrazepam Alprazolam Temazepam Triazolam Diazepam Chlordiazepoxide Oxazepam Lorazepam Alprazolam Diazepam Lorazep Clonazepamam Clobazam

12. Zopiclone Zolpidem Zaleplon Newer nonbenzodiazepine hypnotics

13. Barbiturates are a group of drugs in the class of drugs known as sedative-hypnotics, which generally describes their sleep -inducing and anxiety -decreasing effects. 1. Barbiturate

14. Barbiturates are general depressants for all excitable cells, the CNS is most sensitive where the effect is almost global, but certain areas are more susceptible. CNS Barbiturates produce dose-dependent effects: sedation → sleep → anaesthesia → coma . PHARMACOLOGICAL ACTIONS

15. Hypnotic dose (100–200 mg of a short acting barbiturate) shortens the time taken to fall asleep and increases sleep duration. The sleep is arousable , but the subject may feel confused and unsteady if waken early. Night awakenings are reduced. REM and stage 3, 4 sleep are decreased; REM-NREM sleep cycle is disrupted. The effects on sleep become progressively less marked if the drug is taken every night consecutively Cont.

16. Sedative dose (smaller dose of a longer acting barbiturate) given at daytime can produce drowsiness, reduction in anxiety and excitability Barbiturates can impair learning, short-term memory and judgement . Barbiturates have anticonvulsant property

17. Barbiturates appear to act primarily at the GABA : BZD receptor– Cl ¯ channel complex and potentiate GABA ergic inhibition by increasing the lifetime of Cl ¯ channel opening induced by GABA. At high concentrations, barbiturates directly increase Cl ¯ conductance and inhibit Ca2+ dependent release of neurotransmitters. In addition they depress glutamate induced neuronal depolarization through AMPA receptors(is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system (CNS).) Mechanism of action

18. Respiration is depressed by relatively higher doses. hypercapneic and hypoxic oocurs . CVS Hypnotic doses of barbiturates produce a slight decrease in BP and heart rate, Reflex tachycardia can occur, though pressor reflexes are depressed. Even the dose producing cardiac arrest is about 3 times larger than that causing respiratory failure. Skeletal muscle- Hypnotic doses have little effect but anaesthetic doses reduce muscle contraction by depressing excitability of neuromuscular junction. Sideeffects

19. Smooth muscles Tone and motility of bowel is decreased slightly by hypnotic doses; more profoundly during intoxication. Action on bronchial, ureteric , vesical and uterine muscles is not significant. Kidney Barbiturates tend to reduce urine flow by decreasing BP and increasing ADH release. Oliguria attends barbiturate intoxication .

20. Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal) 1.Long acting drug

21. Phenobarbital acts on GABAa receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal. Mechanism of action

22. Central nervous system effects, such as dizziness, nystagmus and ataxia , are also common. In elderly patients, it may cause excitement and confusion, while in children, it may result in paradoxical hyperactivity . Another rare side effect is amelogenesis imperfecta Side effects

23. Hypersensitivity to any barbiturates Prior dependence on barbiturates Severe respiratory insufficiency Hyperkinesia in children Contraindication

24. Butobarbital ( BAN ), also called butobarbitone or butethal , Soneryl , and Neonal , is a hypnotic drug which is a barbiturate derivative. Butobarital is a barbiturate and is used as a hypnotic. Although it is no longer recommended due to the risk of dependence, tolerance and adverse effects, its continued use may be necessary in severe intractable insomnia in patients already on it 2. Butobarbitone (SHORT ACTING DRUG)

25. Oral Severe intractable insomnia Adult: 100-200 mg at bedtime. Indication

26. Children, young adults, elderly and debilitated patients. Patients with depression or with a history of drug or alcohol abuse or addiction. Insomnia caused by pain. Acute porphyria . Severe hepatic impairment. History of CNS depression or coma, pulmonary insufficiency and sleep apnoea . Pregnancy & lactation. CONTRAINDICATION

27. Drowsiness Ataxia paradoxical excitement confusion headache and CNS depression respiratory depression GI disorders hepatitis Fever megaloblastic anaemia . Potentially Fatal:   Erythema multiforme ; exfoliative dermatitis. ADVERSE EEFECTS

28. Chlordiazepoxide and diazepam were introduced around 1960 as antianxiety drugs. BENZODIAZEPINES (BZDs)

29. Site and mechanism of action Benzodiazepines act preferentially on midbrain ascending reticular formation (which maintains wakefulness) and on limbic system (thought and mental functions). Muscle relaxation is produced by a primary medullary site of action and ataxia is due to action on cerebellum. MECHANISM OF ACTION

30. BZDs act by enhancing presynaptic /postsynaptic inhibition through a specific BZD receptor which is an integral part of the GABAA receptor– Cl ¯ channel complex.

31. The most common side-effects of benzodiazepines are related to their sedating and muscle-relaxing action. drowsiness , dizziness, and decreased alertness and concentration. Lack of coordination may result in falls and injuries. Hypotension and suppressed breathing. changes in appetite, blurred vision, confusion, euphoria , depersonalization and nightmares irritability and suicidal behavior sometimes occur Adverse effects

32. Pregnancy- risk of cleft palate . The symptoms include tremors , hypertonia , hyperreflexia , hyperactivity , and vomiting and may last for up to three to six months. Elderly- Effects such as memory problems daytime sedation impaired motor coordination and increased risk of motor vehicle accidents and falls and an increased risk of hip fractures . Contraindications

33. Diazepam, a benzodiazepine, generates the same active metabolite as chlordiazepoxide and clorazepate . Diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. VALIUM 2, 5, 10 mg tab., 10 mg/2 ml inj. CALMPOSE 5, 10 mg tab, 2 mg/5 ml syr, 10 mg/2 ml inj. HYPNOTICS

34. Benzodiazepines bind nonspecifically to benzodiazepine receptors which mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma- aminobutyric acid-A (GABA A ) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. MECHANISM OF ACTION

35. It Produces an active metabolite which has a long t½, residual effects are likely next morning; cumulation occurs on daily ingestion peaking after 3–5 days; suitable for patients who have frequent nocturnal awakenings. NINDRAL, FLURAZ 15 mg cap. Flurazepam

36. Nitrazepam is a type of benzodiazepine drug. It is a powerful hypnotic drug which possesses strong sedative, anxiolytic , amnestic , anticonvulsant, and skeletal muscle relaxant properties. Nitrazepam shortens the time required to fall asleep and lengthens the duration of sleep. It is also useful for the management of myoclonic seizures. SEDAMON, HYPNOTEX, NITRAVET 5 mg tab., 5, 10 mg cap. Nitrazepam

37. Nitrazepam belongs to a group of medicines called benzodiazepines. It acts on benzodiazepine receptors in the brain which are associated with the GABA receptors causing an enhanced binding of GABA (gamma amino butyric acid) to GABAA receptors. GABA is a major inhibitory neurotransmitter in the brain, involved in inducing sleepiness, muscular relaxation and control of anxiety and fits, and slows down the central nervous system. Mechanism of action

38. The anticonvulsant properties of nitrazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation

39. Alprazolam , a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide , clorazepate , and prazepam , alprazolam has a shorter half-life and metabolites with minimal activity. DOSAGE 0.25 to 0.5 mg orally administered 3 times a day Maximum dose: 4 mg orally administered in divided doses Alprazolam

40. It is an intermediate acting BZD. Absorption is slow in case of tablet but fast when used in soft gelatin capsule. Good for sleep onset difficulty, free of residual effects. Accumulation can occur on daily ingestion. DOSAGE 7.5 to 30 mg orally once a day at bedtime -In transient insomnia , a 7.5 mg dose may be sufficient to improve sleep latency. -In elderly or debilitated patients , therapy should be initiated at 7.5 mg until individual responses are determined. Temazepam

41. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS. Temazepam increases the affinity of the neurotransmitter gamma- aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action.

42. Chlordiazepoxide - Chlordiazepoxide has antianxiety , sedative, appetite-stimulating and weak analgesic actions. The drug seems to block EEG arousal from stimulation in the brain stem reticular formation. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Anti anxiety

43. Mild to moderate anxiety: 5 or 10 mg orally, 3 or 4 times per day Severe anxiety: 20 or 25 mg orally, 3 or 4 times per day DOSAGE

44. Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA receptor. BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization . The net neuro -inhibitory effects result in the observed sedative, hypnotic, anxiolytic , and muscle relaxant properties Mechanism of action

45. Oxazepam is believed to stimulate GABA receptors in the ascending reticular activating system. Since GABA is inhibitory, receptor stimulation increases inhibition and blocks both cortical and limbic arousal following stimulation of the brain stem reticular formation. DOSAGE 10 to 15 mg, 3 or 4 times daily Oxazepam

46. Similar to other benzodiazepines, oxazepam exerts its anxiolytic effects by potentiating the effect of gamma- aminobutyric acid (GABA) on GABA-A receptors through a cooperative mechanism of action. Benzodiazepine binding increases chloride conductance in the presence of GABA by increasing the frequency at which the channel opens. In contrast, barbiturates increase chloride conductance in the presence of GABA by prolonging the time in which the channel remains open. Mechanism of action

47. The α 2 subunit of the α 2 β 3 γ 2 receptor complex is thought to mediate anxiolytic effects while the α 1 subunit of the α 1 β 2 γ 2 receptor complex is thought to mediate sedative, anticonvulsant and anterograde amnesia effects

48. Lorazepam , a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus , and for sedation induction and anterograde amnesia. DOSAGE Initial dose: 2 to 3 mg orally per day administered 2 to 3 times per day Maintenance dose: 1 to 2 mg orally 2 to 3 times a day Parenteral : IV: 2 mg total, or 0.044 mg/kg, whichever is smaller Lorazepam

49. Clonazepamam Clonazepam , a benzodiazepine, is used primarily as an anticonvulsant in the treatment of absence seizures, petit mal variant seizures akinetic and myoclonic seizures, and nocturnal myoclonus ANTI COVULSANT

50. 1.5 mg orally per day divided into 3 doses; this may be increased in increments of 0.5 mg to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maximum dose: 20 mg orally per day DOSAGE

51. Zopiclone This newer cyclopyrrolone hypnotic is an agonist at a subtype of BZD receptor involved in the hypnotic action. The effect on sleep resemble those of BZDs, but it does not alter REM sleep and tends to prolong stages 3 and 4. DOSAGE ZOPITRAN, ZOPICON, ZOLIUM, 7.5 mg tab, one tab at bedtime for not more than 2–4 weeks (elderly 3.75 mg). NON-BENZODIAZEPINE HYPNOTICS

52. Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABA B Z receptor chloride channel macromolecular complex. ACTION

53. Zolpidem is a sedative or hypnotic agent zolpidem in vitro binds the (alpha1) receptor preferentially. The (alpha1) receptor is found primarily on the Lamina IV of the sensorimotor cortical regions, substantia nigra (pars reticulata ), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons , inferior colliculus , and globus pallidus . DOSAGE NITREST, ZOLDEM, DEM 5, 10 mg tabs. Zolpidem

54. This is the shortest acting of the newer non-BZD hypnotics It interacts with the gamma- aminobutyric acid-benzodiazepine (GABA B Z) receptor complex. Subunit modulation of the GABA B Z receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic , muscle relaxant, and anticonvulsive effects in animal models. DOSAGE Dose: 5–10 mg (max 20 mg) at bed time. ZAPLON, ZALEP, ZASO 5, 10 mg tabs. Zaleplon

55. Do not mix intravenous drugs in solution with any other drugs to avoid potential drug-drug interactions. Taper dose as ordered because abrupt withdrawal can precipitate seizure attacks. Provide comfort measures (e.g. small, frequent meals, access to bathroom facilities, orientation, etc.) to help patient tolerate drug effects Provide safety measures (e.g. adequate lighting, raised side rails, etc.) to prevent injuries. Educate client on drug therapy to promote compliance. NURSES RESPONSIBLITY

56. Monitor patient response to therapy (e.g. controlled anxiety, sleep, etc). Monitor for adverse effects (e.g. hypotension , dependence, hepatorenal dysfunction, etc). Evaluate patient understanding on drug therapy by asking patient to name the drug, its indication, and adverse effects to watch for. Monitor patient compliance to drug therapy. EVALUATION

57. SLEEP CLASSIFICATION TYPES NURSES RESPONSIBILITY EVALUATION SUMMARY CONCLUSION