CHAPTER 26 CNS-SEDATIVES AND HYPNOTICS

Barbiturates

* Exert a depressant effect on the CNS. 1.-Action may range from mild sedation to deep anesthesia. 2.-They believed to act primarily by interfering with the chemical transmission of impulses across synaptic junctions within the ascending reticular formation of the brainstem. 3.- Potentiate the inhibitory effects on nerve impluse transmission of a substance known as gamma-aminobutyric acid (GABA-an amino acid found in the CNS)

Safe Nursing Practice Clients Receiving Miscellaneous Sedative-Hypnotics.

1.-Box warnings on the labels of all drugs classified as sedative-hypnotics include a warning about the risk of anaphylaxis, angioedema, and complex sleep-related behaviors. 2.- Client safety must be assured. 3.-Nonbarbiturate, nonbenzodiazepine sedative-hypnotics should be taken only at bedtime and only when the client can devote at least 8 hrs for sleep. 4.-Clients taking nonbarbiturate, nonbenzodiazepines should be monitored for depression. 5.-Clients taking zolpidem should be instructed to take this drug on an empty stomach at bedtime. 6.-The liquid preparation of chloral hydrate should be disguised in juice or milk. 7.-The use of all sedative and hypnotic drugs should be subject to periodic review. 8.-Evaluate client's objectives and subjective responses to use of these drugs and to their withdrawal.

SAFE NURSING PRACTICE CLIENTS RECEIVING BARBITURATES

1.-Box warnings on the labels of all drugs classified as sedative-hypnotics include a warning about the risk of anaphylaxis, angioedema, and complex sleep-related behaviors. 2.-Watch for excessive CNS depression, hypersensitivity reactions, and paradoxical excitement. 3.-Do not mix sodium salts of barbiturates in the same syringe with meperidine HCL. 4.-Avoid using CNS depressants such as alcohol or antihistamines in clients taking barbiturates, and be aware of other possible drug interactions, such as warfarin and anticonvulsants, especially phenytoin. 5.-Barbiturates may be used in suicide attempts. The nurse protects the potentially suicidal client and intervenes promptly whenever barbiturate toxicity is noted. 6.-Barbiturates should be discontinued gradually if they have been used for a prolonged period of time. Abrupt withdrawal may result in seizures.

SAFE NURSING PRACTICE Clients receiving Benzodiazepines

1.-Box warnings on the labels of all drugs classified as sedative-hypnotics include a warning about the risk of anaphylaxis, angioedema, and complex-related behaviors. 2.-as with all sedative-hynoptics, client safety must be assured. 3.-Benzodiazepine hypnotics are contraindicated in pregnancy and should always be slowly withdrawn after prolonged use. 4.-take careful medication history because benzodiazepines have multiple drug interaction. 5.-instruct client not to engaged in activities requiring mental alertness (provide instruction prior to administer benzodiazepine, assist client to he bathroom prior to sedative-hypnotic does) 6.-Watch for excessive CNS depression, hypersensitivity reactions, and paradoxical excitment. 7.-Do not mix IV benzodiazepines in the same syringe with other drugs. 8.-Closely monitor respiratory status during conscious sedation with midazolam. 9.-Benzodiazepines should be discontinued gradually if they have been

Diazepam (valium) (IV, IM, oral) Nursing Implications 3/3

1.-In children 3-8 years of age, the mean half-life of diazepam in 18 hrs. 2.-In full term infants, elimination half-life is 30 hours. 3.-Use contraindicated in children less than 6 months of age, clients with narrow-angle glaucoma, myasthenia gravis, severe respiratory insufficiency, severy hepatic insufficiency, and those with sleep apnea syndrome. 4.-Label warning that this agent should not be used in treatment of phsychotic disorders. 5.-For children, dose must be determined by health care provider and used with caution. 6.-In older adults the elimination half-life "increases by approximately 1 hour for each year of age beginning with a half-life of 20 hours at 20 years of age. 7.-Has amnesic effect when used IM or IV. 8.-IV use for conscious sedation. 9.-IV route is preferred for use during seizure activity. 10.-IM route should be avoided due to the pain caused by the injection.

Diazepam (valium) (IV, IM, oral) Adverse effects 1/3

Adverse Effects Vertigo, dizziness, oversedation, ataxia, confusion.

Estazolam (OP)

Adverse Effects See Diazepam Drug interactions *Alcohol, general anesthetics, antianxiety agents (anxiolytics), antihistamines, CNS depressants, phenothiazines, MAO inhibitors, barbiturates, tricyclic antidepressants, opiod analgesics potentiate CNS depressive effects. *Increases serum levels of digoxin. *Cimeditine, disulfiram, estrogen-containing oral contraceptives, fluoxetine, isoniazid, itraconazole, ketoconazole, protease inhibitor may decrease hepatic metabolism of benzodiazepines causing an increase serum level of benzodiazepines. *Rifampin, theophyl-lines decrease effects of estazolam. Nursing implications see Diazepam

Pentobarbital sodium (Nembutal) (IM, IV) Adverse effects Duration action (short) 1/3

Adverse Effects: Drowsineess, syncope, nervousness, agitation, confusion.

Lorazepam (oral, IM, IV)

Adverse effects see diazepam Drug interactions See diazepam *Concurrent use with clozapine may produce maked sedation, hypotension, ataxia, delirium, and respiratory arrest. *Parenteral lorazepam if used with scopolamine may cause sedation, hallucinations, and behavioral changes. *May increase valproic acid levels. Nursing implications 1.-Administer at bedtime for sleep. 2.-Used for sedation before surgery. 3.-Contraindicated in clients with narrowangle glaucoma. 4.-Used as an antiemetic form breakthrough nausea/vomiting induced by antineoplastic agents. 5.-For IV use, dilute with equal part of 0.9% normal saline or D5W immediately before use. 6.-IV bolus must not exceed 2 mg/min. 7.-If administering IM, inject deep into muscle mass. 8.-Both oral and injectable medication should be refrigerated.

Flurazepam HCL (OP)

Adverse effects see diazepam Drug interactions see diazepam Nursing implication 1.-advise client to avoid activities that require mental alertness while taking this agent. 2.-used as an adjunct for sleep in adults and children 15 years of age and older. 3.-Increased risk of suicidal thoughts and behaviors in adolescents and young adults. 4.-Teratogenic;advise client to discontinue agent immediately if pregnancy occurs.

Secobarbital, Secobarbital Sodium (Seconal Sodium) (Oral) Adverse Effects Duration action (short) 1/3

Adverse effects: see Phenobarbital sodium

Quazepam (Doral) (PO)

Adverse effects: Daytime drowsiness, headache, dizziness, fatigue, dry mouth, dyspepsia. Drug Interactions: See diazepam Increases serum levels of efavirenz, bupropion resulting in CNS toxicities with efavirenz and seizures with burpropion. Nursing implications See diazepam 1.-Contraindicated during pregnancy.

Temazepam (restoril) (PO)

Adverse effects: Drowsiness, fatigue, lethargy, dizziness, hangover, anxiety. Drug interactions see diazepam Nursing implications see diazepam 1.- For short-term treatment of insomnia.

Triazolam (Halcion) (PO)

Adverse effects: See diazepam Drug interactions See diazepam *use contraindicated with ketoconazole, itraconazole, nefazodone. *macrolide antimicrobial agents can increase triazolam serum level by as much as 46% and decrease triazolam's clearance by 53%. *Modafinil, grapefruit juice increase triazolam effects. Nursing implications: *see diazepam *Contraindicated during pregnancy.

BUTABARBITAL SODIUM (ORAL) Adverse effects Duration action (intermediate) 1/3

Adverse effects: Somnolence;other adverse effects occur less than 1% (e.g., agitation, confusion, CNS depression, abnormal thinking, hallucinations, bradycardia, hallucinations, apnea, hypotension, syncope, nausea,vomiting, constipation, headache, hepatotoxicity, skin rash, dizzness, insomnia, anxiety.)

BENZODIAZEPINES

Are a widely used chemical class of drugs employed primarily in the treatment of anxiety. Unlike the barbiturates, these drugs do not appear to significantly suppress REM sleep, and their withdrawal does not result in rebound REM sleep development, although their use can cause the development of tolerance. This makes them more suitable for clients who need prolonged therapy (longer thant 1-2 weeks). Benzodiazepines do not stimulate the production of microsomal enzymes in the liver. This factor permits them to be used safely by clients who are aking drugs metabolized by micosomal enzymes (e.g, warfarin)

Sedatives (also referred as antianxiety agents or anxiolytics)

Are agents that produce a diminished responsiveness to stimuli without producing sleep. Therefore, they reduce anxiety and nervousness, excitability and irritability.

Sedative and hypnotics

Are drugs that depress the CNS by inhibiting transmission of nerve impulses. In doing, so these agents depress the action of many physiological systems and are therefore capable of causing a wide range of desirable and undesirable effects.

Long acting barbiturates (e.g., phenobarbital)

Are primarily used in the treatment of seizure disorders. They may be used as sedatives. They prolonged action reduces the necessity of administering frequent daily doses and maintains a fairly constant blood level throughout the day.

Short - and intermediate-acting barbiturates

Are primarily used in treating insomnia, as they have a rapid onset action (10 -15 minutes) and short duration of action (1 to 6 hrs)

Mention 3 sedative-hypnotics

Barbiturates, benzodiazepines and miscellaneous agents.

How sedative and hypnotics are classified?

Based on the degree of CNS depression they produce.

Barbiturates (tolerance)

Because barbiturates can stimulate their won metabolism, their use for even short periods of time (several days) can result in the development of tolerance, and higher and higher doses of the drug then are required to produce a given pharmacological effect. Experimental evidence has revealed that some of the barbiturate hypnotic agents lose their effectiveness after 2 weeks of continuous use.

Trazodone HCL (PO) Adverse effects: Drowsiness, dizziness, orthostatic hypotension, lightheadedness, nervousness, headache, nausea, vomiting, blurred vision, dry mouth, and insomnia.

Drug Interactions *Increased depressant effects if used concurrently with alcohol, CNS depressants, barbiturates. *Decreases clonidine effects. *Increases serum levels of carbamazepine, digoxin, phenytoin. *May increase or decrease prothrombin times in clients taking warfarin. *Indinavir, itraconazole, ketoconazole, phenothiazines, ritonavir, increase trazodone serum levels. *Use caution if initiating treatment with MAO inhibitors. *Use with SSRIs or venlafaxine can induce serotonin syndrome. Nursing Implications 1.-Non-habit-forming. 2.-As tolerance occurs, dosage may need to be increased in 25 mg increments.

Midazolam (IM,IV) Adverse effects Bronchospasms after IV injection, respiratory depression.

Drug Interactions *Use with alcohol, CNS depressants increases risk of apnea, airway obstruction, oxygen desaturation, hypoventilation. *Decrease dose of nidazolam if used as induction with inhalation anesthesia. *Azole antifungals, aprepitant, clarithromycin, erythromycin, protease inhibitors, SSRIs, fluvoxamine, omeprazole, ranitidine increase effects of midazolam. *Increase sedation if used concurrently with cimetidine, indinavir, ritonavir. Increased hypnotic effects if used concurrently with droperidol, fentanyl, opiod analgesics. *Prolonged half-life if used concurrently with oral contraceptives. *Use with meperidine, antihypertensives, diuretics, lidocaine, paclitaxel increase risk of hypotension. *Increase effects of propofol, digoxin. *Valproic acid decreases liver metabolism of midazolam. * theophyllines antagonize midazolam sedative effects. *Increased CNS depression if used with verapamil. Nursing Implications 1.-Requires continuous respiratory monitoring if given IV. 2.-Label warning: Fulmazenil (specific agent for midazolam reversal) should be available during the time of midazolam use. 3.-Adverse effects most common when drug used for conscious sedation. 4.-Amnesic effect 5.-Avoid IM route when possible. 6.-Label warning: Must be used with extreme caution in higher risk groups (adult and pediatric surgical clients, older adults, debilitated clients, those with COPD)

BUTABARBITAL SODIUM (ORAL) Drug interactions Duration action (intermediate) 2/3

Drug Interactions: Additive effects if used concurrently with alcohol. CNS depressants; Decreases the effects of: warfarin, beta-adrenergic blocking agents, corticosteroids, doxycycline, felodipine, griseofulvin, methadone, metronidazole, nifedipine, quinidine, verapamil, theophyllines, carbazepine, valproic acid, phenytoin, succinimides. Oral contraceptives; Valproic acid, valproate increase the effects of Butabarbital sodium. MAO inhibitors prolong barbiturate effects.

Diazepam (valium) (IV, IM, oral) Drug interaction 2/3

Drug interaction *Alcohol, general anesthetics, antianxiety agents (anxiolitycs), antihistamines, CNS depressants, penotiazines, MAO inhibitors, antipsychotics, barbiturates, tricyclic antidenpressants, opiod analgesics potentiate CNS depressive effects up 48 hours. *Increases serum levels of digoxin, phenytoin, zidovudine *Ritonavir may increase risk of prolonged sedation and respiratory depression so these two agents should not be used concurrently. *Beta-adrenergic blocking agents, cimetidine, disulfiram, estrogen-containig oral contraceptives, fluoxetine, isoniazid, itraconazole, omeprazole, probenecid, valproic acid may decrease hepatic metabolism of benzodazepines causing in increased serum levels of benzodiazepines. *Decreases efffects of levodopa *smoking, theophyllines, rifampin, antacids, decrease effects of diazepam. *Increased risk of hypotension if used concurrently with antihypertensives, CNS depressants, bretylium, lidocaine, paclitaxel, diuretics. *Avoid grapefruit juice.

Pentobarbital sodium (Nembutal) (IM, IV) Drug interaction Duration action (short) 2/3

Drug interaction: Additive effects if used concurrenly with alcohol, CNS depressants; decreaess the effects of warfarin, griseofulvin, beta-adrenergic blocking agents, calcium-channel blocking agents, corticosteroids, succinimides, oral contraceptives, theophyllines, carbamazepine, valproic acid, phenytoin. Valproate, valproic acid increase the effects of barbiturate.

Zaleplon (sonata) (PO) Adverse effects: Headache, dizziness, drowsiness, nausea, dyspepsia, myalgia, eye pain, abdominal pain, asthenia, dysmenorrhea, fever, vertigo, anorexia, epistaxis, changes in vision, malaise.

Drug interaction: *Addictive effects occur if used concurrently with alcohol, CNS depressants, thioridazine. *Rifampin significantly decreases (by 80%) zaleplon effects. *Promethazine, phenytoin, carbamazepine decrease zaleplon effectiveness. *Cimetidine, erythromycin, ketoconazole, significantly increase zaleplon serum levels. Nursing implications: 1.-Assess mental status 2.-Assess potential for abuse. 3.-For use treat insomnia up to 5 weeks. 4.-For clients older than 65 year and for those clients weighing less than 50 kg, dosage should not exceed 10 mg. 5.-Assess for pain and medicate as needed; pain decreases sedative effects. 6.-Caution client to avoid use of alcohol or other CNS depressants. 7.-May cause fetal harm if taken during pregnancy. 8.-Safety and efficacy in children is not established.

Eszopiclone (Lunesta) (PO) Adverse effects: Unpleasant taste, headache, dizziness, drowsiness, dry mouth, dyspepsia, diarrhea, nervousness, somnolence.

Drug interaction: *Clarithromycin, ketoconazole, nefazodone, ritonavir increase eszopiclone serum levels. *CNS depressants including anticonvulsant agents have additive CNS depressants effects. *Use with olanzapine results in decreased psychomotor function. Nursing implications: 1.-Slowed absorption if taken following heavy, high-fat meal. 2.-Instruct client not to discontinue use abruptly. 3.-Assist client to identify triggers that could result in insomnia (caffeine intake, napping, etc.) 4.-Advise client not to engage in activities requiring mental alertness, including driving, after taking eszopiclone. 5.-Administer with a full glass of water on an empty stomach. 6.-Avoid alcohol and OTC medications. 7.-Instruct client not to crush or break tablets.

Secobarbital, Secobarbital Sodium (Seconal Sodium) (Oral) Drug interactions Duration action (short) 2/3

Drug interactions Additive effects if used concurrently with alcohol, CNS depressants; decreases the effects of warfarin, beta-adrenerginc blocking agents, corticosterois, succinimides, oral contraceptives, theophyllines, verapamil, quinidine, carbamazepine, valproic acid

Ramelteon (Rozerem) (PO) Adverse effects: Dizziness, drowsiness, headache, somnolence, nausea, diarrhea, fatigue, insomnia, decreased fertility with prolonged use.

Drug interactions *Azole antifungal agents (e.g.,ketoconazole, fluconazole) may significantly increase the effects of ramelteon. *Alcohol, CNS depressants produce additive depressants effects. *Rifampin decreases effects of ramelteon. *Due to significant (109-fold) increase in ramelteon effects if used with fluvoxamine, these agents should not be used together. Nursing Implications: 1.-Assess for any history of dyspnea, bronchitis, emphysema, sleep apnea, psychiatric disorders, or hepatic disease. 2.-Instruct client to take as directed 30 minutes before going to bed. 3.-Advise client not to engage in activities requiring mental alertness, including driving, after taking ramelteon. 4.-Do not administer with or immediately following a high-fat meal. 5.-Advise client that drug may cause sedation. 6.-Contraindicated in clients with severe hapatic insufficiency.

Zolpidem tartrate (Ambien, Ambien CR) (PO) Adverse Effects: Headache, dizziness, drowsiness, drugged feeling, nausea, diarrhea, dyspepsia, myalgia, URI, nasopharyngitis.

Drug interactions: *Additive effects occur if used concurrently with alcohol, CNS depressants, chlorpromazine. *Azole antifungal agnets increase zolpidem levels. *Flumazenil reverses zolpidem effects. *Causes decrease in the peak serum level of imipramine. *Rifampin decreases zolpidem levels. *17% increase in zolpidem half-life if used concurrently with fluoxetine. *Use with ritonavir can result in severe sedation and respiratory depression. *SSRIs shorten the onset of zolpidem. *Sertraline decreases zolpidem serum level by 53%. Nursing implications: 1.-Initial dose of 5 mg should be used in older adult clients. 2.-Food delays the hypnotic action of the drug.

Chloral hydrate (noctec, etc) (PO, rectal) Adverse effects: Drowsiness, dizziness, orthostatic hypotension, lightheadedness, nervousness, ataxia, residual sedation ("hangover effect"), disorientation, abuse, dependence, cardiac arrhythmias, respiratory failure, fatal hypertension.

Drug interactions: *Increased depressant effects if used concurrently with alcohol, CNS depressants, barbiturates. *IV furosemide if administered within 24 hrs of chloral hydrate can result in diaphoresis, flushing, tachycardia, and hypertension. *may increase bleeding if used concurrently with warfarin. *Decreases effects of phenytoin. Nursing implications 1.-Take oral doses with full glass of liquid after meals to minimize gastrointestinal upset. 2.-Store oral dosage forms in a dark container. 3.-Dosage of oral anticoagulants may need to be adjusted.

Nonbezodiazepines and nonbarbiturates

Have become quite popular as sleep aids. Although these agents are not benzodiazepines. They act on the GABA similarly to barbiturates and benzodiazepines. These agents; however, the incidence of adverse effects from these medications is much less common than with either barbiturates or benzodiazepines.

Alcohol (ethanol)

It is a CNS depressant, and should be avoid by clients receiving other CNS depressant drugs, those with a history of alcohol abuse, and clients who have recently experienced head trauma.

Sedative-hypnotics

Many drugs can act as either sedatives or hypnotics, depending on the dose administered and are therefore sometimes referred to as sedative-hypnotics

BENZODIAZEPINES USED AS HYPNOTIC AGENTS

NOTE: 1.-Monitor clients for vertigo, dizziness, and oversedation. 2.-Monitor for effectiveness. 3.-Monitor children and older adults closely because adverse effects are most likely to occur in this clients. 4.-Provide for client safety by use of siderails, assistance with ambulation, and instruction to avoid activities requiring mental alertness. 5.-Benzodiazepines can exert by teratofenic (first trimester) and nonteratogenic effects (third trimester). 6.-Monitor carefully in clients who are suicidal, depressed, or known drug abusers. 7.-When used for conscious sedation (e.g; midazolam, diazepan), continuous respiratory monitoring shuould be done. 8.-Closely monitor digoxin levels.

BARBITURATES USED AS SEDATIVE AND HYPNOTICS

NOTE: 1.- Avoid the use of other CNS depressants. 2.-Provide for the clients's safety through the use of side-rails, assistance with ambulation, and instruction to avoid activities requiring mental alertness. 3.- Monitor drug use very carefully in depressed, suicidal, or confused clients and in known drug abusers. 4.- Monitor for drug abuse and dependence. 5.-Doses of oral anticoagulants and phenytoin (anticonvulsant) may need to adjusted. 6.-Prolonged used of barbiturates may increase vitamin D requirements. 7.-Watch for toxicity, including confusion, excitement, deep sleep, coma, pupil constriction, cyanosis, clammy skin and hypotension. *Drug dosages should be tapered off gradually. *Abrupt withdrawal can lead to seizures and death. *Older adult and debilitated clients may be more sensitive to barbiturates. Dosage reduction may be required. *Record observations about the effectiveness of these agents.

Nonbarbiturates and Nonbenzodiazepines/sedative-Hypnotic Agents

Note: *Avoid using with other CNS depressants. *Provide for client safety by use of siderails, assistance with ambulation, and instruction to avoid activities requiring mental alertness. *Monitor carefully in clients who are suicidal, depressed, or known drug abusers. *Reevaluate for comorbidities if use extends beyond 10 days. *Monitor for risk of severe anaphylactic reactions. *Advise clients of risk of abnormal thinking and behavior including sleep-driving. *Record observations about the effectiveness of these agents.

BUTABARBITAL SODIUM (ORAL) Nursing Implications Duration action (intermediate) 3/3

Nursing Implications: *Originally approved in 1939 *If phenytoin and butabarbital are administered concurrently, serum levels of both agents must be monitored frequently.

Pentobarbital sodium (Nembutal) (IM, IV) Nursing implications Duration action (short) 3/3

Nursing Implications: 1.-When using IV, use large vein and do not exceed infusion rate of 50 mg/mi 2.- Monitor closely for extravasation as tissue necrosis may occur. 3.-IM injections should be given deeply into a large muscle mass to prevent pain and abscess formation. 4.-Do not mix in same syringe with meperidine HCL. 5.- Do not confuse pentobarbital sodium with phenobarbital sodium. 6.-Do not use parenteral solutions if precipitate is present. 7.-Use parenteral solution within 30 minutes after preparation

Secobarbital, Secobarbital Sodium (Seconal Sodium) (Oral) Nursing implications Duration action (short) 3/3

Nursing implications Only oral form is manufactured in the United States.

The barbiturates enjoyed wide popularity because

Of their versatility in providing actions that range in duration from several seconds to as long as 24-36 hrs but but benzodiazepines (e.g., midazolam) have replaced their use with anesthesia because they are more predictable and have fewer adverse effects.

Hypnotics

Tend to have a more intense depressant effect on the CNS and usually produce sleep.

Barbiturates withdrawl

The severity of withdrawal manifestations generally is dependent on the dosage and duration of administration prior to withdrawal, as well as how abruptly the drug is discontinued. Rapid withdrawal of the drug from a client who has used high and frequent doses for extended periods of time may produce severe convulsions and death.

Nonprescription sleep aids.

Virtually all of theses products contain an antihistamine that exerts a depressant effect on the CNS to produce sedation. Clients using nonprescription sleep aids including herbals should be advised to use caution in engaging in hazardous tasks while using this medications. Clients should be instructed to seek medical assistance if insomnia persist for more than 2 weeks. Nonprescription sleep aids should not be used by clients with asthma or glaucoma without a health care provider advice. Clients using these drugs should be cautioned to avoid the use of alcohol or other CNS-depressant drugs because these may interact with the nonprescription sleep aids.

ultra short-acting barbiturates are used

primarily as IV anesthetics, usually in combination with an inhalational agent. Their duration of action may be as brief as several seconds, thereby permitting close control of a client during surgery

The failure of insomnia to remit after 7 to 10 days of treatment may idicate:

the presence of a primary psychiatric and or medical illness that should be evaluated

Warning box (sedative-hypnotics)

warning about the risk of anaphylaxis, angioedema, and complex sleep-related behaviors.