SEDATIVES

Sedative [anxiolytic] -Reduces anxiety -Little or no effect on motor or mental functions -Suppression of responsiveness to a constant level of stimulation -Decreased spontaneous activity and ideation

Hypnotic -Produces drowsiness -Encourage onset and maintenance of sleep .

SEDATIVE – HYPNOTIC DRUGS .

Zolpidem Indication & Dosage Oral Short-term management of insomnia Adult: As conventional release tab: 10 mg immediately before bedtime. Activated charcoal may be given if presented within one hour of ingestion of >100 mg zolpidem in adults and >5 mg in children. Elderly: As conventional tab: Initiate with a 5-mg dose before bedtime.) Overdosage Symptoms: impairment of consciousness from somnolence to coma. . Severe: contra-indicated. Administration Should be taken on an empty stomach. compromised CV and respiratory function. Management: Treatment is largely symptomatic and supportive.1. Gastric lavage may be considered if presented within 1 hr of ingestion of >100 mg zolpidem. (Do not take w/ or immediately after a meal. but generally not needed.5 mg immediately before bedtime. As controlled release tab: 6. As controlled release tab: 12. max: 10 mg/day.25 mg immediately before bedtime. Hepatic impairment: As conventional tab: Initiate with 5 mg before bedtime. Haemodialysis unlikely to be useful. Flumazenil may be used if there is severe CNS depression.

drugged feelings. hepatic impairment. ataxia. vomiting. Caution in patients exhibiting symptoms of depression. sleep-driving (driving while not fully awake after drug ingestion. confusion. Zolpidem Contraindications Special Precautions Severe hepatic insufficiency. myasthenia gravis. Potentially Fatal: Hepatitis. euphoria. back pain. nausea. drowsiness. abnormal thinking and behaviour. hiccups. Patients should be warned from doing any work involving mental alertness or motor coordination after ingestion of the drug. . Obstructive sleep apnoea. with no recollection of the event). anaphylactic reactions. compromised respiratory function.1. Pregnancy and lactation. diplopia. Adverse Drug Reactions Storage Oral: Store at 20-25°C (68-77°F). diarrhoea. vertigo. abnormal vision. insomnia. Max duration of treatment: 4 wk including tapering. Re-evaulate if insomnia fail to remit after 7-10 days. Amnesia. dizziness.

Elimination half life: 2. Used as hypnotics and sedatives. Distribution: Protein binding: 92%. Peak plasma concentration: 3 hr.zolpidem . Excretion: Excreted in urine and faeces as inactive metabolites. . Food reduce both the rate and extent of GI absorption. metabolised primarily by the cytochrome P450 isoenzyme CYP3A4. Zolpidem has a rapid onset but short duration of hypnotic action.1.5 hr. MIMS Class ATC Classification Hypnotics & Sedatives N05CF02 . It has a selective affinity to BZD receptors prevalent in the cerebellum (omega-1 receptors). Belongs to the class of benzodiazepine related agents. Absolute bioavailability: 70%. Metabolism: Undergoes first pass metabolism. Distributed into breast milk. It has strong sedative actions but only minor anxiolytic properties. Absorption: Rapidly absorbed from GI tract. It has also less effects on skeletal muscle and seizure threshold. Zolpidem Mechanism of Action Zolpidem acts by binding to the benzodiazepine (BZD) receptors of the GABA receptor complex.

irritability. Bromisoval Indication & Dosage Oral Sedation Adult: 0. Contraindications Elderly and debilitated patients. vit K deficiency symptoms. hypersensitivity reactions. Porphyria. GI disturbances. Elderly and debilitated patients. resp depression. Special Precautions Renal insufficiency. haematologic disorders. pulmonary insufficiency. Adverse Drug Dependence. Potentially Fatal: Bromide accumulation and symptoms resembling bromism. preexisting CNS depression or coma.2. child. sedation. may impair ability to drive or operate machinery. depression. ataxia. Pregnancy and lactation. congenital malformations when taken during pregnancy. young adults. sleep apnoea. slurred speech and ataxia in excessive doses.2-1 g at night. severe hepatic impairment. may cause paradoxical excitatory reaction when given to patients in pain unless an analgesic is given concomitantly. paradoxical excitement. Reactions headache. Produces neonatal intoxication. young adults and childn. miosis. confusion and memory defects. . skin reactions. Nystagmus. drowsiness.

influenza vaccination and vitamins. John's wort. vigabatrin. antidepressants eg. thereby antagonise the anticonvulsant action of barbiturates. bupropion. Others: Fenoprofen. digitoxin. lidocaine and quinidine. furosemide. Alcohol. methadone. Mechanism of Action MIMS Class ATC Classification . teniposide. doxycycline.2. levothyroxine. tiagabine and zonisamide. valproate and progabide. HIV-protease inhibitors. a bromureide which in turn have general properties similar to barbiturates. St. chlorpromazine. corticosteroids. calcium-channel blockers eg. chloramphenicol. MAOIs may prolong the CNS depressant effects and also reduce the convulsive threshold. theophylline. pethidine and opioid analgesics. oxcarbazepine. βblockers. ethosuximide. It was formerly used for its sedative and hypnotic properties. Hypnotics & Sedatives N05CM03 . clonazepam. metronidazole. fluoxetine. disopyramide.bromisoval . nifedipine and verapamil. Bromisoval has actions and uses similar to carbromal. lithium and mianserin. griseofulvin. oral contraceptives. montelukast. warfarin and coumarin. lamotrigine. Bromisoval Drug Interactions Sedation or resp depression may be enhanced by drugs with CNS depressants. ciclosporin. carbamazepine. Belongs to the class of other hypnotics and sedatives.

May be given rectally if oral route is not available. 1 mth-12 yr: 30-50 mg/kg (max: 1 g). Child: Neonate: 30-50 mg/kg. Pregnancy and lactation. suicide tendencies. oesophagitis. Contraindications Hepatic or renal impairment. up to 100 mg/kg (max: 2 g) may be used. or whose history indicates they may increase dosage on their own . 12-18 yr: 1-2 g. Special Precautions May impair ability to drive and operate machinery. or a history of alcohol and drug abuse. 1218 yr: 0. gastritis. up to 100 mg/kg may be used with respiratory monitoring. Dose to be taken at night. May be given rectally if oral route is not available.3. Oral Sedation Adult: 250 mg tid.5-2 g as a single dose at night. Doses to be taken 45-60 minutes before procedure. porphyria. Patients with mental depression. Elderly: Dose reduction may be required. Max: 2 g daily Child: Neonate: 30-50 mg/kg.5-1 g (max: 2 g). cardiac disease. Chloral hydrate Indication & Dosage Oral Insomnia Adult: 0. Elderly: Dose reduction may be required. 1 mth-12 yr: 30-50 mg/kg (max: 1 g). hypersensitivity.

Reddy. headache. ataxia. Additive CNS depression with other CNS depressants such as paraldehyde.g. rashes. vertigo. malaise. barbiturates. lightheadedness. Drug Interactions Lab Interference . nightmares. eosinophilia. Chloral hydrate may produce false-positive results for urine-glucose determination utilizing cupric sulfate e. Chloral hydrate Adverse Drug Reactions Gastric irritation. dependence on prolonged use. ketonuria. reduction in white blood cell count. delirium (especially in elderly). It may interfere with fluorometric tests for urine catecholamines. Furosemide or oral anticoagulants may increase the risk of side effects. except urine glucose tests utilising glucose oxidase. Alcohol. Benedict's solution and possibly with cupric sulfate tablets.3. Jenkins. staggering gait. excitement. and Thron procedure for determining urinary 17-hydroxycorticosteroids. abdominal distention and flatulence.

Some is also excreted via the bile. liver and other tissues. Metabolism: Rapidly metabolised to trichloroethanol and trichloroacetic acid in the erythrocytes. Drugs should be given only if the potential benefit justifies the potential risk to the foetus. Its CNS depressant effect. Belongs to the class of aldehydes and derivatives.3. effective only for short-term use. Distribution: Passes into the CSF. breast milk and across the placenta. . Onset: 30-60 min.chloral hydrate . Chloral hydrate Pregnancy Category Category C: Either studies in animals have revealed adverse effects on (US FDA) the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. trichloroethanol. Mechanism of Chloral hydrate is used principally as a hypnotic in the treatment of Action insomnia. may be attributed to its metabolite. Absorption: Rapidly absorbed from the GI tract after oral admin. Excretion: Partly excreted in the urine as trichloroethanol and its glucuronide (urochloralic acid) and as trichloroacetic acid. Duration: 4-8 hr. MIMS Class Hypnotics & Sedatives ATC Classification N05CC01 . similar to those of paraldehyde and barbiturates. Used as hypnotics and sedatives.

Hepatic impairment: Initiate at lower dose and adjust slowly.5 mg tid. . Elderly: and debilitated patients: Initiate at lower dose and adjust slowly. Oral Epilepsy Adult: 90 mg daily in divided doses. Elderly: and debilitated patients: Initiate at lower dose and adjust slowly. Elderly: and debilitated patients: Initiate at lower dose and adjust slowly.4. clorazepate Available Brand: Tranxene Indication & Dosage Oral Anxiety Adult: 7. Oral Alcohol withdrawal syndrome Adult: 90 mg daily in divided doses. Child: 9-12 yr old: 60 mg in divided doses. Hepatic impairment: Initiate at lower dose and adjust slowly. Child: 9-12 yr old: 60 mg in divided doses. Hepatic impairment: Initiate at lower dose and adjust slowly.

seizures. Treatment is symptomatic and supportive. history of drugdependence.4. patients experiencing apnoea during sleep. alcoholics. Monitor pulse. child <9 yr. renal impairment. hepatic disease. Haemodialysis is not likely to be useful. resp disease. clorazepate Overdosage Somnolence. narrow-angle glaucoma. lactation. slurred speech. If recent ingestion. and diminished reflexes. confusion. emesis or gastric lavage followed by activated charcoal and a saline cathartic to remove any remaining drug. respiratory depression and apnea also may occur. Flumazenil. . Patients with depressive or psychotic disorders. patients on CNS depressant or psychoactive drug therapy. depression. IV norepinephrine or metaraminol may be used for hypotension. Pregnancy. Contraindications Hypersensitivity (cross-sensitivity with other benzodiazepines may occur). impaired coordination. may be used after evaluating the benefits and risks. respiration and blood pressure. esp those with suicidal tendencies. hypotension. coma. Admin IV fluids and maintain an adequate airway. impaired gag reflex. Special Precautions Elderly. debilitated patients. operating machines or driving. a benzodiazepine antagonist.

Herbs or nutraceuticals eg. antihistamines. cimetidine. lightheadedness. nervousness. extrapyramidal disorders. CYP3A4 inhibitors eg. Grapefruit juice increases serum conc or toxicity risk of clorazepate. rash. insomnia. blurred vision. hypotension. St. xerostomia.4. clorazepate Adverse Drug Reactions Jaundice. kava kava and gotu kola may increase CNS depression upon concomitant admin with clorazepate. tremor. headache. ethanol. decreased salivation. clarithromycin may increase serum conc and toxicity of clorazepate. dizziness. MAO Inhibitors. anxiety. Carbamazepine. depression. ataxia. Potentiates CNS effects of narcotic analgesics. drowsiness. acute attacks of porphyria in porphyric patients. confusion. ciprofloxacin. dysarthria. amprenavir. increased or decreased appetite. vomiting. constipation. valerian. nausea. John's wort. sedativehypnotics. memory impairment. diplopia. barbiturates. fatigue. decreased libido. irritability. hepatic necrosis. diarrhoea. slurred speech. Drug Interactions Food Interaction . rifampin and rifabutin may decrease clorazepate therapeutic effects by enhancement of clorazepate metabolism. phenothiazines. cyclic antidepressants.

limbic system. clorazepate Pregnancy Category (US FDA) Storage Mechanism of Action Category D: There is positive evidence of human foetal risk.g. hepatic (as active oxazepam). Clorazepate binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron within the central nervous system. but the benefits from use in pregnant women may be acceptable despite the risk (e. Absorption: Following oral administration. Oral: Store at 15-30°C. reticular formation resulting to an increase in chloride ion permeability which further leads to hyperpolarisation and stabilisation. Metabolism: Rapidly activated to desmethyldiazepam via decarboxylation prior to absorption at low stomach pH. Excretion: Via urine.. Onset: 1-2 hrs.4. Distribution: Crosses the placenta and small amounts appear in the urine. Duration: 8-24 hrs. complete absorption of the dose from the small intestine. Hypnotics & Sedatives / Anticonvulsants MIMS Class . if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

up to 2. Oral Premedication in surgery Child: ≥6 mth: Single dose of 250-500 mcg/kg. Max total: 7. up to a max of 20 mg. midazolam Indication & Dosage Oral Short-term management of insomnia Adult: 7. Younger patients (6 mth-<6 yr) may require up to 1 mg/kg. Elderly: 20-50 mcg/kg given 20-60 minutes before surgery by deep IM inj. 5-10 minutes before procedure.5-15 mg given at night.5-5 mg. Parenteral Sedation for dental and minor surgical procedures Adult: IV admin: Initially. Younger patients (6 mth-<6 yr) may require up to 1 mg/kg. Repeat after at least 2 minutes if necessary. Usual total: 3. .5 mg. Oral Sedation for dental and minor surgical procedures Child: ≥6 mth: Single dose of 250-500 mcg/kg. up to a max of 20 mg. Child: ≥1 yr: 80-200 mcg/kg given 20-60 minutes before surgery by deep IM inj.5 mg given over at least 2-5 minutes.5. Intramuscular Premedication in surgery Adult: 70-100 mcg/kg (usual dose: 5 mg) given 20-60 minutes before surgery by deep IM inj.

Intravenous Sedation in critical care Adult: Loading dose: 30-300 mcg/kg given as infusion over 5 minutes to induce sedation. Elderly: 100-200 mcg/kg in divided doses at 2-minute intervals. and reduce maintenance dose. IM admin (used only in exceptional cases): 1-15 yr: 50-150 mcg/kg. max: 10 mg. increase slowly at 2-minute intervals up to a total of 600 mcg/kg. . Max total: 500 mcg/kg (not >25 mg). Elderly: Initially 1-1. midazolam Indication & Dosage Child: IV admin: 6 mth-5 yr: Initial: 50-100 mcg/kg given over 2 minutes.5 mg given over 2 min. max total dose: 10 mg. Child: >7 yr: 150 mcg/kg. increased by increments of 0. hypovolaemia or vasoconstriction: Reduce or omit loading dose. Maintenance dose: 20-200 mcg/kg/hr. Additional doses may be required to complete induction. For patients with hypothermia. up to 600 mcg/kg in resistant cases. max total dose: 6 mg.5.5-1 mg at 2 min intervals as needed. Intravenous Induction of anaesthesia Adult: 150-200 mcg/kg by slow inj in premedicated patients and at least 300 mcg/kg for those who have not received a premedicant. 6-12 yr: 25-50 mcg/kg given over 2 minutes and increase slowly at 2-minute intervals up to a total of 400 mcg/kg.

Elderly: Dosage may need to be reduced. Rectal Premedication in surgery Child: >6 mth: 300-500 mcg/kg as a single dose. The inj solution may be diluted with Water for Injections up to a total volume of 10 ml if the volume is too small.5. Rectal Sedation for dental and minor surgical procedures Child: >6 mth: 300-500 mcg/kg as a single dose. midazolam Indication & Dosage Child: Neonates with gestational age <32 wk: 30 mcg/kg/hr by continuous IV infusion. ≥6 mth: Initial loading dose of 50-200 mcg/kg given by slow IV inj. May dilute with water for inj up to a total volume of 10 mL if the volume is too small. calculate dose based on ideal wt. vasoconstriction or hypothermia. . maintenance dose of 60-120 mcg/kg/hr given as IV infusion. Neonates with gestational age >32 wk and who are <6 mth: 60 mcg/kg/hr. Reconstitution: Midazolam solution for injection may be administered rectally. Special Populations: Dosage in intensive care may need to be reduced in patients with hypovolaemia. In obese paediatric patients. May dilute with water for inj up to a total volume of 10 mL if the volume is too small.

Acute pulmonary insufficiency or marked neuromuscular respiratory weakness including unstable myasthenia gravis. confusion. Acute narrow-angle glaucoma. Caution should be observed in the use of flumazenil in case of mixed drug overdosage and in patients with epilepsy already treated with benzodiazepines. Symptoms of overdose include sedation. acute alcohol intoxication. More serious symptoms would be areflexia. intrathecal and epidural admin. hypotension. Treatment is generally supportive and symptomatic. coma or patients in shock. midazolam Administration Overdosage May be taken with or without food. muscle relaxation or paradoxical excitation. apnoea and coma. severe respiratory depression. Contraindications .5. impaired coordination. The benzodiazepine antagonist flumazenil is indicated in cases of severe intoxication accompanied with coma or respiratory depression. cardiorespiratory depression.

neonates. airway obstruction. cardiac disease. respiratory disease. laryngospasm. headache. apnoea. anaphylaxis. nystagmus. history of drug or alcohol abuse. jaundice. vomiting. avoid prolonged use or abrupt withdrawal. euphoria. titrate dose carefully. elderly and debilitated (reduce dose). cardiac arrest. post-operative sedation. lactation Physical and psychological dependence with withdrawal symptoms. Pregnancy. or apnea. May impair ability to drive or operate machinery. thrombosis. hallucinations. oversedation. severe fluid or electrolyte disturbances. ataxia. Potentially Fatal: Respiratory depression. Adverse Drug Reactions . hepatic impairment. increased appetite. anterograde amnesia. decreased tidal volume and respiration rate. skin rash. seizure-like activity (paediatrics). myasthenia gravis. monitor for early signs of hypoventilation. bronchospasm. respiratory arrest. heart rate changes. fatigue. reduced alertness. midazolam Special Precautions Paediatric patients with cardiovascular instability. chronic renal failure. confusion. hiccup. cough. dizziness. kernicterus.5. pruritus. hypotension. open-angle glaucoma. paradoxical reactions. nausea.

. erythromycin.9% sodium chloride or 5% dextrose in water. barbiturates. phenobarbital. quinupristin with dalfopristin. verapamil. antiretroviral agents.9% sodium chloride or 5% dextrose in water. Increased respiratory depression with opiates. Parenteral: Store at 20-25°C. Intramuscular: Store at 20-25°C. thiopental requirements may be reduced during concurrent use. Bioavailability of oral midazolam increased by grapefuit juice. midazolam is stable for up to 24 hr when diluted with 0. phenobarbital. rifampicin. Avoid concomittant use. midazolam is stable for up to 24 hr when diluted with 0. if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).g. midazolam is stable for up to 24 hr when diluted with 0. Halothane.5 mg/ml. clarithromycin. other sedatives and anaesthetics. other benzodiazepines. carbamazepine.5. midazolam Drug Interactions Increased CNS depression with alcohol. but the benefits from use in pregnant women may be acceptable despite the risk (e. Intravenous: Store at 20-25°C. Rectal: Store at 20-25°C.5 mg/ml. Plasma concentrations increased by CYP3A4 inhibitors such as cimetidine. Category D: There is positive evidence of human foetal risk.5 mg/ml.9% sodium chloride or 5% dextrose in water. Midazolam concentration decreased by phenytoin. ketoconaz ole and itraconazole. At a final concentration of 0. opioids. Food Interaction Pregnancy Category (US FDA) Storage . At a final concentration of 0. diltiazem. At a final concentration of 0.

anxiolytic and anticonvulsant actions. prolonged in neonates. elderly and hepatic impairment. the hypnotic/anaesthetic action may be due to the occupation of the benzodiazepine and GABA receptors leading to membrane hyperpolarisation and neuronal inhibition. Distribution: Crosses the placenta. and further interfering with the re-uptake of GABA at the synapses. MIMS Class ATC Classification . peak plasma concentrations after 20-60 min (depending on route). Absorption: Rapidly absorbed (any route). It exerts sedative and hypnotic. Protein-binding: 96% Metabolism: Extensively hepatic via CYP3A4 isoenzyme.midazolam .5. 2 hr (elimination half-life). muscle relaxant. Used as hypnotics and sedatives. Anxiolytics / Hypnotics & Sedatives / Anticonvulsants N05CD08 . While the probable anxiolytic action might be as a result of the drug's ability to increase glycine inhibitory neurotransmitter level. midazolam Mechanism of Action Midazolam is a short-acting benzodiazepine. Excretion: Urine (as glucuronide conjugates). Belongs to the class of benzodiazepine derivatives. converted to hydroxymethylmidazolam. enters breast milk.

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