sedative hypnotic poisoning

Sedative-Hypnotic Drugs Sedative-Hypnotic Drugs

Dr.Peer Mohamed.MDDr.Peer Mohamed.MDAsst Professor,Asst Professor,

Dept. of Medicine,Dept. of Medicine,Madurai Medical CollegeMadurai Medical College

• Anxiolytic: drug that reduce anxiety

• Sedatives: drugs that have an inhibitory effect on the CNS; reduce nervousness, excitability and irritability without causing sleep

• Hypnotics: drugs that have more potent effects than sedatives; cause sleep

• Sedative – hypnotics: drugs that can act in the body either as a sedative or hypnotic

Sedative – Hypnotics: ClassificationSedative – Hypnotics: Classification

1. Barbiturates

2. Benzodiazepines

3. Newer Agents: zolpidem, zaleplon, eszopiclone, ramelteon, buspirone

Sedative – Hypnotics: Clinical UsesSedative – Hypnotics: Clinical Uses

• for relief of anxiety

• for insomnia

• for sedation and amnesia before and during medical and surgical procedures

• for treatment of epilepsy and seizure states

Sedative – Hypnotics: Clinical UsesSedative – Hypnotics: Clinical Uses

• as component of balanced anesthesia

• for control of ethanol or other sedative-hypnotic withdrawal states

• for muscle relaxation in specific neuromuscular disorders

• as diagnostic aids

BarbituratesBarbiturates

• introduced into clinical use in 1903

• derivatives of barbituric acid

• produce many unwanted side effects: habit-forming and have a narrow therapeutic range

Barbiturates: ClassesBarbiturates: Classes

Ultrashort• onset: <15 minutes• duration: <2 hours• mephobexital, thiamylal, thiopental

Short• onset: 15 – 20 minutes• duration: 2 -4 hours• pentobarbital, secobarbital

Intermediate• onset: 20 – 30 minutes• duration: 2 – 4 hours• aprobarbital, butabarbital

Long• onset: 30 – 60 minutes• duration: 6 – 8 hours• phenobarbital


Pharmacokinetics• most barbiturates are absorbed rapidly following oral

administration• all sedative-hypnotics cross the placental barrier; are also

detectable in breast milk

Biotransformation• only phenobarbital is excreted unchanged in the urine


Mechanism of Action

• inhibit nerve impulse transmission by potentiating GABA (increase the duration of the GABA-gated chloride channel openings; direct activation of the GABA-chloride channels)

• CNS depressant

• act primarily on the reticular formation


Therapeutic Uses

1. hypnotics2. sedatives3. anticonvulsant4. anesthesia adjuncts5. reduction of intracranial pressure in neurosurgical

patients (ultrashort)6. treatment of neonatal hyperbilirubinemia (long)


Side Effects and Adverse Effects

CNS: drowsiness, lethargy, dizziness, excitement, paradoxical restlessness, headache, depression

CVS: vasodilatation and hypotension (if given rapidly)Blood: decreased rbc, wbc and plateletsGIT: nausea, vomiting, diarrhea, constipationRespiratory: respiratory depression, laryngospasm, bronchospasm, coughingOther: allergic reactions: rashes, fever, Stevens – Johnson syndrome


Toxicity and Management of Overdose

• overdose: 1. respiratory depression respiratory arrest 2. CNS depression: sleep coma and death

• treatment: symptomatic and supportive

• activated charcoal to help eliminate the drug


Interactions

• produces additive CNS depression with: 1. alcohol 2. antihistamines 3. benzodiazepines 4. opioids

• prolonged effect if given with: 1. MAOIs 2. anticoagulants


Drug Profiles

• dosage forms: tablets, capsules, elixirs, injections, suppositories

• pregnancy category: D

• all are considered as controlled substances

• contraindications: hypersensitivity, significant liver dysfunction, known previous addiction

PhenobarbitalPhenobarbital

Luminal

• most frequently prescribed

barbiturate• long – acting agent

Uses:1. seizures2. hyperbilirubinemia3. Gilbert’s syndrome

Contraindications:1. preexisting CNS

depression2. severe pain3. severe respiratory

disease

Routes of Administration1. PO2. IM3. IV

PhenobarbitalPhenobarbital

Lifespan Considerations

• readily crosses placenta; distributed in breast milk

• may cause postpartum hemorrhage or hemorrhagic disease in newborns

• elderly may exhibit confusion, excitement

PentobarbitalPentobarbital

Nembutal

Uses:1. hypnotic (insomnia)2. preop med3. anticonvulsants4. treatment for withdrawal symptoms

SecobarbitalSecobarbital

Seconal

Uses:1. hypnotic agent2. status epilepticus3. anesthetic adjunct

BenzodiazepinesBenzodiazepines

• most frequently prescribed sedative–hypnotic

• safe

• anxiolytic or sedative–hypnotic


Long Actingflurazepamquazepam

Short Actingestazolamtemazepamtriazolam

(Dalmane)(Doral)

(Prosom)(Restoril)(Halcion)


Pharmacokinetics• rate of oral absorption depends on lipophilicity; triazolam –

extremely rapid• lipid solubility also determines the rate of entry into the

CNS

Metabolism• metabolic transformation to more water-soluble

metabolites• major site of metabolism is the liver

• Excretion• via the kidneys

BenzodiazepinesBenzodiazepinesMechanism of Action

• binding to GABA receptors potentiation of GABAergic inhibition

• depress specific areas of the brain: 1. hypothalamus 2. thalamus 3. limbic system

• no suppression of REM


Drug Effects

• calming effect on the CNS

• controlling agitation and and anxiety

• skeletal muscle relaxation

Therapeutic Uses

• sedation

• sleep induction

• anxiety relief

• alcohol withdrawal

• epilepsy


Effects on Patterns of Normal Sleep

1. the latency (time to fall asleep) of sleep onset is decreased

2. the duration of stage 2 NREM sleep is increased

3. the duration of REM is decreased

4. the duration of stage 4 NREM slow-wave sleep is decreased


Side/Adverse Effects

• drowsiness• headache• paradoxical excitement/ nervousness• dizziness• vertigo• lethargy• palpitations• dry mouth• nausea and vomiting

Toxicity and Overdose

• somnolence• confusion• coma• diminished reflexes

Treatment• symptomatic and supportive• gastric lavage• Flumazenil


Drug Profiles

• C IV controlled substances

• pregnancy category X agents

• contraindications: hypersensitivity and pregnancy

FlurazepamFlurazepam

Dalmane

• Long – acting hypnotic agent

• For short term treatment of insomnia (may be used up to 4 weeks)

• “hangover” effect: lethargy or grogginess

TemazepamTemazepam

Restoril

• indication: short-term treatment of glaucoma

• contraindication: patients with glaucoma

Newer AgentsNewer Agents

Zolpidem (Ambien)

• imidazopyridine• absorbed rapidly into the blood following oral

administration• reaches peak plasma levels in 1.6 hours• metabolized in the liver• mechanism of action: similar to benzodiazepines (binds

selectively to GABA receptors• uses: short-term treatment of insomnia (7-10 days)• toxicity: extension of CNS depressant effect• interaction: ethanol

RamelteonRamelteon

• Rozerem• mechanism of action: agonist at MT1 and MT2 melatonin

receptors in the suprachiasmatic nuclei of the brain• no direct effect on GABA neurotransmission• rapidly absorbed after oral administration and undergoes

extensive first-pass metabolism• prescribed specifically for patients who have difficulty in

falling asleep• adverse effects: dizziness, somnolence, fatigue,

decreases in testosterone and increases in prolactin• not a controlled substance

BuspironeBuspirone

• BuSpar• relieves anxiety without marked sedative, hypnotic or

euphoric effects• has no anticonvulsant or muscle relaxant properties• anxiolytic effect may take more than one week to become

established not suited for management of acute anxiety states

• does not interact directly with the GABAergic system• rapidly absorbed orally and undergoes extensive first pass

metabolism• does not potentiate effects of conventional sedative-

hypnotics

BZD-ADVERSE DRUG BZD-ADVERSE DRUG REACTIONREACTION

•Acute toxicity: Benzodiazepines in acute overdose are considerably less dangerous than other sedative-hypnotic drugs. Cause prolonged sleep,without serious depression of respiration or cardiovascular. The availability of an effective antagonist, flumazenil.

BZD-ADVERSE DRUG BZD-ADVERSE DRUG REACTIONREACTION

• Side-effects during therapeutic use: drowsiness, confusion, amnesia, impaired coordination. Main disadvantages are interaction with alcohol, long-lasting hangover and the development of dependence.

• Tolerance and dependence: induction of hepatic drug-metabolising enzymes; a change at the receptor level;

Barbiturates-Adverse Barbiturates-Adverse effectseffects

• After effect: hangover---dizzy, drowsiness, amnesia, impaired judgment, disorientation.

• Tolerance: decreased responsiveness to a drug following repeated exposure because of down-regulation of receptors and induction of hepatic drug-metabolising enzymes.

Barbiturates-Adverse Barbiturates-Adverse effectseffects

• Dependence: including psychologic and physiologic dependence. Withdrawal symptoms: excitation, insomnia, tremor, anxiety, hallucinations and sometimes convulsions.

• Depressant effect on respiration: can cross the placental barrier during pregnancy and secrete to breast milk.

• Others: Skin eruptions and porphyria

Treatment of acute Treatment of acute overdosageoverdosage

• An overdose can result in coma, diminished reflexes, severe respiratory depression, hypotension leading to cardiovascular collapse, and renal failure.

• Treatment (A.B.C): (1) supporting respiration and circulation. (2) alkalinizing the urine and promoting

diuresis. (3) Hemodialysis or peritoneal dialysis.

Thank You!

sedative hypnotic poisoning

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