22 sedative hypnotic drugs

Post on 20-Aug-2015

2,628 views 6 download

Tags:

transcript

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

Anita Q. Sangalang, MD, FPOGSFACULTY OF PHARMACY

UNIVERSITY OF SANTO TOMAS

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTICS

Benzodiazepines Barbiturates Miscellaneous agents

Short Ultra

action action

Intermediate Short Buspirone

action action Chloral hydrate

Long Long Zaleplon

action action Zolpidem

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

SEDATION• Reduction of anxiety• Calming effectANXIOLYTIC• Drug that reduces anxiety• SedativeHYPNOSIS• Induction of sleep

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

• Lipid soluble

• Absorbed well from the GIT

• Good distribution to the brain

• Metabolized before elimination from the body by hepatic enzymes

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Converted initially to active metabolites with long half-lives

• Diazepam and flurazepam After several days of therapy

accumulation of active metabolites can lead to excessive sedation

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Lorazepam and oxazepam Undergo extrahepatic conjugation

and do not form active metabolites

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Bz receptors Form part of GABAA receptor-chloride

ion channel macromolecular structure Binding facilitates the inhibitory actions

of GABA Increased GABA mediated chloride ion

conductance

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Flumazenil Reverses the CNS effects of

benzodiazepines Antagonist at the Bz receptor

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Beta-carbolines High affinity for Bz receptors Can elicit anxiogenic and convulsant

effects Inverse agonists

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Diazepam

desmathyldiazepam active

oxazepam metabolites

conjugation

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BENZODIAZEPINES

• Chlorazepam

• Estazolam immediately converted to • Oxazepam inactive metabolites

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Extensively metabolized

• Depress the neuronal activity

• Facilitates and prolongs the inhibitory effects of GABA and glycine

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Bind to multiple isoforms of GABAA

receptor but at different sites from those with which benzodiazepines interact

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Not antagonize by flumazenil

• Increase the duration of GABA- mediated chloride ion channel opening

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Block the excitatory transmitter glutamic acid and at high concentration, sodium channels

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Thiopental Drug with highest lipid solubility enter

the CNS rapidly Used as induction agents in anesthesia

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Thiopental CNS effects are terminated by rapid

redistribution of the drug from the brain to other highly perfused tissues (skeletal muscles)

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Thiopental Metabolism occur via oxidation

and glucoronidation Converted to active metabolite

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

BARBITURATES

• Phenobarbital Goes to the liver to be oxidized Excreted partly unchanged in the urine Alkalinizes the urine Half-life of 4-5 days Requires loading dose

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

OTHER DRUGS

• Buspirone Partial agonist at serotonin receptor

(5-HT receptor) Impairment of mental activity Psychomotor impairment Selective with minimal depressant

effects on the CNS

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

OTHER DRUGS

• Zolpidem and zaleplon Exert their CNS effects via interaction

with benzodiazepine receptors Bind more selectively Antagonize by flumazenil

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

DRUG A - BARBITURATES dose = CNS depression

DRUG B - BENZODIAZEPINES - flatter dose response curve - greater margin of safety

DRUG A

DRUG B

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS1. Sedation2. Hypnosis• Promote sleep onset• Increase the duration of the sleep stateSTAGES OF SLEEPa. REM (Rapid eye movement)• Dream• Decreases at high dosesb. Non-REM• 70-75%

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS3. Anesthesia• Thiopental (barbiturate)• Midazolam (benzodiazepine)• Loss of consciousness, amnesia

and suppression of reflexes

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS4. Anticonvulsant actions• Phenobarbital, clonazepam

Suppression of seizure activity Selective because they do not

cause severe sedation

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS4. Anticonvulsant actions• Diazepam, lorazepam and phenobarbital

Given IV Used in status epilepticus Heavy sedation is needed

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS5. Muscle relaxation• Diazepam

Spasticity states Cerebral palsy

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS6. Medullary depression• High doses can lead to

Respiratory arrest Hypotension CVS collapse Death in suicidal overdose

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS

7. Tolerance and dependence

• Tolerance Decrease in responsiveness Used chronically or in high dosage

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS

7. Tolerance and dependence

• Tolerance Metabolic tolerance

Occurs with phenobarbital Induces its own metabolism Decreases CNS response to the

drug itself

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS

7. Tolerance and dependence

• Dependence

Physiologic State of response to a drug Removal of the drug evokes

unpleasant symptoms Opposite of the drug’s effects

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS

7. Tolerance and dependence

• Dependence

Physiologic Leads to abstinence syndrome

(withdrawal state) when the drug is discontinued

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN –SYSTEM EFFECTS7. Tolerance and dependence• Dependence

Physiologic Withdrawal signs

Anxiety Tremors Hyperreflexia Seizures

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS

7. Tolerance and dependence

• Dependence

Physiologic Occur more commonly with short-

acting drugs Pentobarbital and secobarbital Dependence is unlikely to occur

with buspirone

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

ORGAN SYSTEM EFFECTS7. Tolerance and dependence• Dependence

Psychological State of response to a drug Drug taker feels compelled to use

the drug Suffers anxiety when separated

from the drug

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

CLINICAL USES1. Anxiety states• Benzodiazepines with intermediate or

long durations of action are favored• Buspirone

Used for generalized anxiety disorders• Alprazolam

Phobic and panic attacks

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

CLINICAL USES2. Sleep disorders• Used to treat primary insomnia and

other sleep disorders

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

CLINICAL USES3. Sedation • Prior to medical/surgical procedures• Conscious sedation-anterograde

amnesia4. Treatment of seizures and convulsions

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

CLINICAL USES4. Detoxification of alcoholics• Chlordiazepoxide• Diazepam6. Muscle relaxation7. Manias, major depression, phobias

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

TOXICITY

1. Psychomotor dysfunction

• Cognitive impairment

• Decreased psychomotor skills

• Unwanted daytime sedation

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

TOXICITY

2. Additive CNS depression

• When used with Alcoholic beverages Antihistamines Antipsychotic drugs Opioid analgesics Tricyclic antidepressants

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

TOXICITY

3. Overdosage causes severe respiratory and cardiovascular depression

4. Terratogenic

SEDATIVE-HYPNOTIC DRUGS

SEDATIVE-HYPNOTIC DRUGS

TOXICITY

3. Induce formation of liver microsomal enzymes

• Metabolize drugs multiple drug interactions

• Chloral hydrate displaces coumarin from protein binding sites and increases anticoagulant effects