CNS Depressant

Name of Drug

Pentobarbital

Dosage

Adult : PO Hypnotic 100-200 mg at bedtime. Sedation 20-40 mg 2-4 times daily. IV Hypnotic Initial:
100 mg, then increase to 200-500 mg. IM Hypnotic 150-200 mg. Rectal Hypnotic 120-200 mg.

Mechanism of Action

Description: Pentobarbital is a barbiturate mainly used as a sedative and hypnotic. It has been
suggested that its pharmacologic effect is due to its property to enhance the activity of GABA by altering
GABA receptor-mediated inhibitory synaptic transmissions.
Onset: Oral/Rectal: 15-60 min; IV: 1 min; IM: 10-25 min.
Duration: Oral/Rectal: 1-4 hr; IV: Approx 15 min.
Pharmacokinetics:
Absorption: Well absorbed in the GI tract. Time to peak plasma concentration: 30-60 min.
Distribution: Plasma protein binding: Approx 60-70%.
Metabolism: Hepatic metabolism mainly by hydroxylation to inactive metabolite.
Excretion: Via urine as hydroxypentobarbital. Plasma half-life: 1st phase: Approx 4 hr; 2nd phase: 35-50
hr.

Indication

Listed in Dosage.

Contraindication

Bronchopneumonia, severe pulmonary impairment. History of porphyria and addiction to sedative and
hypnotics. Concomitant Na oxybate.

Drug to drug interaction

Additive effect w/ other CNS depressants. Increased plasma concentrations w/ MAO inhibitors. May
decrease serum levels of phenytoin, carbamazepine, valproic acid. May increase metabolism of
anticoagulants, corticosteroids, griseofulvin, doxycycline and hormonal contraceptives.
Potentially Fatal: Increased sleep duration and CNS depression w/ Na oxybate.

Drug to Food Interaction

Increased CNS depression w/ alcohol.

Adverse Drug Reaction

Drowsiness, somnolence, dizziness, anxiety, insomnia; hypotension, apnoea, resp depression,

bronchospasm, laryngospasm, bradycardia, CNS depression, physical and psychological dependence,
psychiatric disturbance, confusion, hallucinations, nightmares, thinking abnormality, syncope,
hyperkinesias, ataxia, agitation, nervousness, nausea, vomiting, constipation, pain at inj site.
Potentially Fatal: Stevens-Johnson syndrome.

Nursing Considerations

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Name of Drug

Butabarbital
Dosage

Adult : PO 100-200 mg at bedtime.

Mechanism of Action

Description: 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.
Pharmacokinetics:
Distribution: About 26% bound to plasma proteins.
Metabolism: Hepatically mainly via hydroxylation.
Excretion: Small amount excreted unchanged in urine. Half-life: about 40 hr.

Indication

Severe intractable insomnia.

Contraindication

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.

Drug to drug interaction

Butobarbital is a potent liver enzyme inducer and may reduce the effect of coumarin for up to 6 wk. Additive CNS
depression with alcohol. Reduced effect of tricyclic antidepressants (such as amitriptyline, clomipramine,
desipramine, dosulepin, imipramine, melitracen etc), corticosteriods (such as hydrocortisone, dexamethasone etc),
coumarins, darifenacin, disopyramide, doxorubicin, metronidazole, theophylline and tolvaptan. It is also likely that the
drug level of lidocaine is reduced due to the increased liver enzyme activity. May reduce drug level of memantine.
Increased sedation with thalidomide.
Potentially Fatal: Concurrent long-term use with phenmetrazine may result in psychosis. Concurrent use with
sodium oxybate is contraindicated due to the additive CNS depressant effect. Butobarbital is a potent inducer of
CYP3A4 and is expected to reduce the AUC of gefitinib significantly.

Drug to Food Interaction

Avoid alcohol.

Adverse Drug Reaction

Drowsiness, ataxia, paradoxical excitement, confusion, headache and CNS depression; respiratory depression; GI
disorders; hepatitis: fever; megaloblastic anaemia.
Potentially Fatal: Erythema multiforme; exfoliative dermatitis.

Nursing Considerations

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Name of Drug

Flurazepam
Dosage

Adult : PO 15-30 mg at night.

Mechanism of Action

Description: Flurazepam is a long-acting benzodiazepine which binds to stereospecific benzodiazepine receptors on

the postsynaptic GABA neuron w/in the CNS, including the limbic system, reticular formation. It enhances the
inhibitory effect of GABA on neuronal excitability by increasing neuronal membrane permeability to Cl ions, thus
resulting in hyperpolarisation and stabilisation.
Onset: Hypnotic: 15-20 min.
Duration: 7-8 hr.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. Time to peak plasma concentration: Approx 30-60 min.
Distribution: Crosses the placenta. Volume of distribution: 3.4 L/kg. Plasma protein binding: Approx 97%.
Metabolism: Undergoes hepatic metabolism to N-desalkylflurazepam (active) and N-hydroxyethylflurazepam.
Excretion: Via urine (mainly as conjugated metabolites). Elimination half-life: 2.3 hr (parent drug).

Indication

Insomnia.

Contraindication

Patient w/ pre-existing CNS depression or coma, resp depression, acute pulmonary insufficiency, myasthenia gravis,
sleep apnoea, chronic psychosis or obsessional states. Pregnancy.

Drug to drug interaction

May enhance CNS depressant effect w/ antidepressants, antipsychotics, general anaesth, hypnotics or sedatives,
opioid analgesics. Flurazepam clearance may be reduced by cimetidine, and may be increased by rifampicin.

Drug to Food Interaction

May increase CNS depression w/ alcohol and St John's wort. May increase serum levels w/ grapefruit juice.

Adverse Drug Reactions

Increased risk of hazardous sleep-related activities (e.g. sleep-driving), drowsiness, light-headedness, dizziness,
confusion, anterograde amnesia, headache, fatigue, reduced alertness, numbed emotions, apnoea, dyspnoea,
muscle weakness, ataxia, slurred speech, double vision, vertigo, hypotension, skin rashes, GI and visual
disturbances, excessive salivation, changes in libido, urinary retention.

Nursing Considerations

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Name of Drug

Fentanyl
Dosage

Adult : Buccal Breakthrough cancer pain Patients already receiving and tolerant to opioid treatment: As loz: Initial:
200 mcg over 15 min per episode; may repeat once after 15 min if needed. Max: 1.6 mg/dose. No more than 4 unit
doses should be taken daily. As tab: Initial: 100 mcg per episode; may repeat once after 30 min if needed; wait for at
least 2 or 4 hr before treating another episode. As film: Initial: 200 mcg per episode; thereafter, at least 2 hr must
elapsed before treating another episode. Sublingual

Mechanism of Action

Description: Fentanyl is a potent opioid analgesic that increases pain threshold, alters pain reception and inhibits
ascending pain pathways by binding to stereospecific receptors w/in the CNS.
Onset: IV: Rapid; IM: Approx 7-15 min; Transdermal (initial placement): 6 hr; Transmucosal: 5-15 min.
Duration: IV: 30-60 min; IM: 1-2 hr; Transdermal (removal of patch/no replacement): 72-96 hr.
Pharmacokinetics:
Absorption: Transmucosal: Rapidly absorbed from buccal and nasal mucosa, the remainder is swallowed and slowly
absorbed from the GI tract. Transdermal: Slow absorption after application. Bioavailability: Buccal film: 71%; buccal
tab: 65%; lozenge: Approx 50%; sublingual spray: 76%; sublingual tab: 54%. Time to peak plasma concentration:
Buccal film: 0.75-4 hr; sublingual spray: 10-120 min; sublingual tab: 15-240 min; transdermal patch: 20-72 hr.
Distribution: Highly lipophilic, distributes rapidly from blood into the lungs and skeletal muscles then into deeper fat
compartments. It crosses the placenta, enters the breast milk and appears in the CSF. Volume of distribution: 4-6
L/kg. Plasma protein binding: Approx 80%.
Metabolism: Hepatic via N-dealkylation and hydroxylation by CYP3A4 isoenzyme..
Excretion: Via urine (75%, primarily as metabolites; <7-10% as unchanged drug); faeces (approx 9%). Elimination
half-life: IV: 2-4 hr; transdermal patch: 20-27 hr; transmucosal: 3-14 hr (dose-dependent); nasal spray: 15-25 hr.

Indication

Listed in Dosage.

Contraindication

Opioid nontolerant patient. Treatment of acute pain other than breakthrough pain (e.g. migraine or other headaches)
or post-op pain; acute or severe resp depression or obstructive lung disease; paralytic ileus.

Drug to drug interaction

Concomitant use w/ CYP3A4 inhibitors (e.g. erythromycin, clarithromycin, troleandomycin, azole antifungals, ritonavir,
amiodarone, nefazodone, aprepitant, diltiazem and verapamil) increases serum levels of fentanyl and may potentiate
fatal resp depression. Increased risk of life-threatening serotonins syndrome w/ SSRIs, SNRIs and MAOIs. May
reduce serum levels w/ rifamycin derivatives. Enhanced depressant effect w/ general anaesth, tranquilisers,
barbiturates and narcotics. May increase excretion w/ ammonium Cl. May increase hypotensive effect w/
phenothiazines. May reduce efficacy of pegvisomant.

Drug to Food Interaction

May enhance depressant effect w/ alcohol. Serum levels may be increased by grapefruit juice. May reduce serum
levels w/ St John's wort.

Adverse Drug Reaction

Reduce pulmonary compliance and/or apnoea, bronchoconstriction, laryngospasm; nausea, vomiting; bradycardia,
oedema, CNS depression, confusion, dizziness, drowsiness, headache, sedation, hypotension, peripheral
vasodilation, increased intracranial pressure, itching, rash, erythema, papules, pruritus, exfoliative dermatitis,
pustules, macular rash; gum bleeding and irritation, taste perversion, dental caries, tooth loss, gum line erosion;
throat irritation, nasal ulcers, epistaxis, rhinorrhoea; coughing; urinary retention.
Potentially Fatal: Resp depression.

Nursing Considerations

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Name of Drug

Diazepam

Dosage

Adult : PO Severe anxiety 2-10 mg 2-4 times daily depending on the severity of symptoms.

Mechanism of Action

Description: Diazepam is a long-acting benzodiazepine that exerts anxiolytic, sedative, anticonvulsant, muscle
relaxant and amnestic effect. It binds to stereospecific benzodiazepine receptors on the postsynaptic gamma-
aminobutyric acid (GABA) neuron in different regions of the central nervous system, e.g. brain and spinal cord
thereby, increasing the inhibitory effects of GABA which is involved in sleep induction, control of hypnosis, memory,
anxiety, epilepsy and neuronal excitability.
Onset: Status epilepticus: 1-3 mins (IV); 2-10 mins (rectal).
Duration: Status epilepticus: 15-30 mins.
Pharmacokinetics:
Absorption: Readily and completely absorbed from the gastrointestinal tract or after rectal administration. Delayed
and decreased absorption with a moderate fat meal. Bioavailability: >90%. Time to peak plasma concentrations:
Approx 30-90 minutes (oral); approx 10-30 minutes (rectal). approx 1 min (IV); 0.25-2 hours (IM).
Distribution: Crosses the blood-brain barrier and placental barrier; redistributed into fat depots and tissues. Enters
breast milk. Volume of distribution: 1.1 L/kg (oral); 1.2 L/kg (IV); 1 L/kg (rectal). Plasma protein binding: 98% (oral);
95-98% (rectal).
Metabolism: Metabolised in the liver via N-demethylation by CYP3A4 and CYP2C19 to N¬-desmethyldiazepam,
hydroxylation by CYP3A4 to temazepam and further metabolised to oxazepam.
Excretion: Via urine (mainly as glucuronide conjugates). Elimination half-life: 44-48 hours (oral); 33-45 hours (IV);
approx 60-72 hours (IM); 45-46 hours (rectal).

Indication

Listed in Dosage.

Contraindication

Acute or chronic severe respiratory insufficiency, respiratory depression, myasthenia gravis, sleep apnoea, severe
hepatic insufficiency, acute narrow-angle glaucoma, phobic or obsessional states, chronic psychosis, hyperkinesis,
acute porphyria. Avoid alcohol. Infants <6 months.

Drug to drug interaction

Potentiated effects with other centrally acting agents (e.g. antipsychotics, anxiolytics, anticonvulsants, antihistamines,
MAO inhibitors, anaesthetics, barbiturates). Enhanced sedative effect with other drugs such as lofexidine, nabilone,
and disulfiram. Reduce clearance and potentiate action with CYP3A4 inhibitors (e.g. cimetidine, isoniazid,
erythromycin, omeprazole, ketoconazole). Increased metabolism and clearance with CYP3A4 inducers (e.g.
rifampicin, carbamazepine, phenytoin). Antagonised effect with theophylline. Delayed absorption with antacids.
Potentially Fatal: Concomitant use with opioids may result in sedation, respiratory depression, coma and death.
Increased risk of prolonged sedation with zidovudine. May enhance CNS depressant effect of sodium oxybate.

Drug to Food Interaction

Reduced sedative and anxiolytic effects with caffeine. Increased plasma concentration with grapefruit or grapefruit
juice. Decreased serum concentration with St John’s wort. Enhanced CNS depressant effect with alcohol.

Adverse Drug Reaction

Significant: Withdrawal symptoms (e.g. rebound insomnia and anxiety, panic, palpitations, sweating, paranoid
psychosis, epileptic attacks, delirium), anterograde amnesia, paradoxical reactions (e.g. restlessness, agitation,
irritability, aggressiveness, delusion, rages, nightmares, psychoses), habituation, drug dependence.
Eye disorders: Blurred vision, diplopia.
Gastrointestinal disorders: Constipation, nausea, gastrointestinal disturbances, altered salivation.
General disorders and admin site conditions: Fatigue, ataxia, local reactions at the injection site e.g. thrombophlebitis
and venous thrombosis.
Investigations: Elevated transaminases and alkaline phospahatase.
Nervous system disorders: Impaired motor ability, tremor, headache, vertigo.
Psychiatric disorders: Confusion, depression, slurred speech.
Renal and urinary disorders: Urinary incontinence, urinary retention.
Reproductive system and breast disorders: Change in libido.
Vascular disorders: Hypotension.

Nursing Considerations

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Name of Drug

Thiopental Sodium

Dosage

Adult : IV Induction of anesth As 2.5 or 5% soln: 100-150 mg, repeat every 30-60 sec if needed. Max: 500 mg. Max
in pregnant women: 250 mg. Status epilepticus W/ assisted ventilation: As 2.5% soln: 75-125 mg. Reduction of
raised intracranial pressure Intermittent bolus inj of 1.5-3.5 mg/kg, if adequate ventilation is provided.

Mechanism of Action

Description: Thiopental sodium, a short-acting barbiturate anaesthetic, is a CNS depressant inducing hypnosis and
anaesthesia but not analgesia. It has also been used in the control of refractory tonic-clonic status epilepticus and to
reduce increased intracranial pressure in neurosurgical patients.
Onset: IV: 30 sec. Rectal: 8-10 min.
Pharmacokinetics:
Distribution: Crosses the placenta and enters breast milk. Protein-binding: 80%
Metabolism: Hepatic; mostly converted to inactive metabolites.
Excretion: Elimination half-life: 10-12 hr (adults); 6 hr (childn); 26-28 hr (obese and pregnant patients).

Indication

Listed in Dosage.

Contraindication

Porphyria; dyspnoea or respiratory obstruction.

Drug to drug interaction

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action
with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and
excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased
requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other
highly protein bound drugs.
Potentially Fatal: Increased resp depression with opioids.

Drug to Food Interaction

Use of valerian, kava kava or St John's wort may prolong effect of thiopental. All herbal medicines should be stopped
2 wk prior to elective surgery.

Adverse Drug Reaction

Coughing, hiccupping, sneezing, muscle twitching, laryngospasm, bronchospasm. IV: tissue necrosis (if extravasation
occurs). Intra-arterial: Severe arterial spasm with burning pain, blanching of forearm and hands and gangrene of
digits.
Potentially Fatal: Respiratory depression, arrhythmias, circulatory failure and anaphylactoid reactions.

Nursing Considerations

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Name of Drug

Fentanyl
Dosage

Mechanism of Action

Indication

Contraindication

Drug to drug interaction

Drug to Food Interaction

Adverse Drug Reaction

Nursing Considerations

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