(Ch 19) Sedative-Hypnotic and Anxiolytic Flashcards
What are CNS Depressants?
CNS depressants are medications that suppress the transmission of information throughout the central nervous system.
What are the 7 Classifications of CNS Depressants
There are 7 classifications of CNS depressants.
They are:
- Sedative-hypnotics
- General and local anesthetics
- Analgesics
- Narcotic analgesics 5. Anticonvulsants
- Antipsychotics
- Antidepressants
Define anxiety:
Ex of symptoms involved:
An unpleasant emotional state consisting of apprehension, tension, and feelings of danger without a real or logical cause
Tachycardia- Tachypnea -Sweating -Trembling Weakness
What are the 4 major classes of drugs used to treat anxiety?
1. Benzodiazepines—the most frequently used drugs for anxiety, most important group, used as sedative and hypnotic agents.
2. Azapirones—(5-HT 1a receptor agonist, ex: Buspirone) are a class of drugs used as anxiolytics, antidepressants, and antipsychotics.
They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs
3. Barbiturates—rarely used today because of severe side effects and a low therapeutic index. These drugs have generally been replaced by the benzodiazepines.
4. β -adrenoceptor antagonists (e.g. propranolol). They are used to treat some forms of anxiety,
where physical symptoms (sweating, tremor, and tachycardia), are troublesome. They are not used as hypnotics.
Ex: Benzodiazepines and their approximate duration of action:
Short-Acting
Short-Acting (2 to 8 hr):
- Triazolam (Halcion)
- Oxazepam (Serax)
- Midazolam (Versed)
- Clonazepam (Klonopin)
Ex: Benzodiazepines and their approximate duration of action:
Intermediate-Acting
Intermediate-Acting (10 to 20 hr):
- Temazepam (Restoril)
- Lorazepam (Ativan)
- Alprazolam (Xanax)
- Alprazepam
Ex: Benzodiazepines and their approximate duration of action:
Long-Acting
Long-Acting (1 to 3 days):
1. Chlordiazepoxide (Librium)
2. Diazepam (Valium)
3. Flurazepam (Dalmane)
4. Clonazepam
Benzodiazepines:
Bind strongly to what ?
Are inactivated by what ?
Benzodiazepines are well absorbed when given orally.
- They bind strongly to plasma proteins, however, many of them accumulate gradually in the body fat (i.e. they are highly lipid soluble).
- Benzodiazepines are inactivated by the liver and excreted in the urine.
Benzodiazepines:
Pharmacodynamics ?
Pharmacodynamics
Act by binding to a specific regulatory site on the GABAA receptor, thus enhancing the inhibitory effects of GABA. Central nervous system effects of benzodiazepines include:
- Reduction of anxiety and aggression.
- Sedation and induction of sleep.
- Reduction of muscle tone and coordination.
- Anticonvulsant effects
Benzodiazepines
Clinical Uses:
Clinical Uses
Treatment insomnia
Anxiety
Preoperative mediations
Acute alcohol withdrawal
As anticonvulsants
Chronic muscle spasm and spasticity
Benzodiazepines:
Side-effects
Side-effects
Toxic effects due to acute overdosage causes prolonged sleep.
Side-effects occurring during normal therapeutic use includes:
drowsiness, confusion, amnesia, and impaired motor coordination.
Tolerance and dependance: Pharmacokinetic and tissue tolerance and also cause physical dependance.
i.e. stopping benzodiazepines treatment after weeks or months causes an increase in symptoms of anxiety.
Benzodiazepine
Pharmacokinetic:
Pharmacokinetic:
Absorbed from GI tract; crosses blood– brain barrier; metabolized in liver, and excreted in urine
What is GABA?
GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter of the CNS.
How do benzodiazepines work?
- When benzodiazepines bind to specific receptors that are separate from but adjacent to the GABAA receptor, they potentiate the binding of GABA to its own receptor.
- The binding of GABA to its own receptor results in increased chloride ion conductance, cell membrane hyperpolarization, and decreased initiation of action potentials.
Remember that benzodiazepines do not bind to GABA receptors—they bind adjacent to them
What are the therapeutic indications for benzodiazepines?
Name 4
These drugs are used clinically as muscle relaxants and in the treatment of the following:
1. Anxiety disorders
2. Panic disorders—alprazolam is the drug of choice.
Status epilepticus—diazepam is the drug of choice.
3. Sleep disorders—flurazepam or temazepam.
4. Alcohol withdrawal—diazepam is most commonly used.
Are benzodiazepines effective for controlling pain as well as anxiet?
No. They have little analgesic effect.
Benzodiazepine:
What is their route of administration?
PO, IV, or IM
Where are benzodiazepines metabolized?
They are metabolized in the liver and excreted in the urine. Many of the benzodiazepines have active metabolites.
Does dependence occur?
Yes. Prolonged use can result in dependence. Abrupt discontinuation can result in withdrawal symptoms, including confusion, anxiety, and agitation.
What types of symptoms may a patient taking benzodiazepines experience?
- Drowsiness and confusion—the most common side effects: Ataxia (loss of full controll of bodily movements) Dizziness
- Respiratory depression and death if taken with other CNS depressants such as ethanol
What are Sedative-hypnotics?
Ex:
Sedative-hypnotics (Benzodiazepines) , the mildest form of central nervous system depressant, are given in low doses to diminish physical and mental responses without affecting consciousness.
Short-acting sedative-hypnotics are prescribed to help fall asleep, allowing the patient to awake early without a lingering after effect.
Intermediate-acting sedative-hypnotics are used for sustaining sleep and have residual drowsiness after waking.
NOTE: Sedative-hypnotics are not prescribed for patients who have severe respiratory disorders or who are pregnant.
Sedative-hypnotics are prescribed for short-term use because the patient can develop a tolerance of and dependency on the medication. Avoid chronic use of sedative-hypnotics.
5 - HT1A receptor agonist
- Provide Ex:*
- Define:*
- SE:*
Buspirone
is a potent agonist of. 5 - HT1A receptors. Anxiolytic effects take days to weeks to develop.
- Buspirone does not cause sedation*, motor incoordiation and withdrawal effects.
- The main side effects*: are nausea, dizziness, headache, and restlessness.
Schedule IV: Drugs
- Benzodiazepine’s:*
- Examples? 5*
- Flurazepam hydrochloride (Dalmane)
- Diphenhydramine (Benadryl)
- Temazepam (Restoril)
- Triazolam (Halcion)
- Zolpidem (Ambien)
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV:
Use:
- Short-term treatment of insomnia* (up to 4 weeks); a. a. reduces sleep induction time
b. reduces number of nocturnal awakenings; increases length of sleep.
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV:
How it works:
• Enhances action of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), producing hypnotic effect caused by CNS depression
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV:
Adult dose
1• Flurazepam hydrochloride (Dalmane) 15–30 mg at bedtime (15 mg for elderly)
2• Zolpidem (Ambien): PO 10 mg at bedtime (elderly, debilitated 5 mg)
3• Triazolam (Halcion): PO 0.125–0.5 mg at bedtime (elderly 0.0625–0.125 mg)
4• Temazepam (Restoril): PO 15–30 mg at bedtime (elderly 7.5–15 mg)
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV:
Administration
- Give without regard to meals.
- Capsules may be emptied and mixed with food.
- Triazolam (Halcion): Tablets may be crushed and grapefruit juice may alter absorption.
- Zolpidem (Ambien): For faster sleep onset, do not give with or immediately after a meal.
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV:
Contraindications:
• Narrow-angle glaucoma, acute alcohol intoxication, and pregnancy. Use with caution with impaired liver or kidney function.
SEDATIVE–HYPNOTIC–BENZODIAZEPINE–SCHEDULE IV: (control substances)
Side effects / Adverse reactioins
SE• Drowsiness, dizziness, ataxia, sedation. Morning drowsiness may occur initially. Occasionally GI disturbances, nervousness, blurred vision, dry mouth, headache, confusion, skin rash, irritability, and slurred speech
AR• Hangover, REM Rebound, dependence, tolerance, excessive depression, respiratory depression, hypersensitivity
What is flumazenil’s MOA?
Flumazenil is a competitive antagonist of benzodiazepines at the GABAA receptor.
Describe the clinical use of Flumazenil drug.
Reversal of benzodiazepine sedation or overdose
How is Flumazenil administered to the patient
IV use only
How long do the effects of flumazenil last?
Only 1 hr—Repeat doses may be necessary for a heavily sedated patient to remain alert.
AZAPIRONES: BUSPIRONE (BuSpar)
How does buspirone work?
It acts as a partial agonist at serotonin (5- HT1A) receptors.
AZAPIRONES: BUSPIRONE (BuSpar)
What are the indications for this drug?
Buspirone is used for generalized anxiety;
however, unlike benzodiazepines,
its effects may take 1 to 2 weeks to become apparent.
AZAPIRONES: BUSPIRONE (BuSpar)
What are the pharmacokinetic properties of buspirone?
This drug is metabolized by the liver and excreted in the urine;
its half-life is 2 to 11 hr.
AZAPIRONES: BUSPIRONE (BuSpar)
How do the actions of buspirone differ from those
of the benzodiazepines?
Buspirone lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines.
AZAPIRONES: BUSPIRONE (BuSpar)
What advantages does buspirone have over benzodiazepines?
- Minimal sedation
- Low abuse potential
- No overdose fatalities reported
- No withdrawal symptoms
AZAPIRONES: BUSPIRONE (BuSpar)
What toxic effects are associated with buspirone?
Headache, nausea, dizziness
Define Barbituates:
They are non-selective CNS depressants, which produce effects ranging from sedation and reduction of anxiety, to unconsciousness and death from respiratory and cardiovascular failure.
BARBITURATES act by:
Barbiturates act by enhancing action of GABA,
- but less specific than benzodiazepines.
- They are potent inducers of hepatic drug metabolizing enzymes, hence likely to cause drug interaction.
- Tolerance and dependance occur, more than benzodiazepines
BARBITURATES are classified as?
Specifically USED for WHAT and are able to control WHAT condition?
Classified as type of Sedative-Hypnotic
Use: to induce sleep and as an anesthetic.
-In high doses barbiturates control epileptic seizures.
Barbiturates are considered what Class of Drugs and by duration of Action.
Class of Drugs?
Name the Durations of Action?
Barbiturates are Class II controlled substances prescribed for no more than two weeks because of adverse side effect such as CNS depression in the elderly.
Barbiturates are classified by duration of action.
- Ultrashort-acting: Ultra–short-acting barbiturates (thiopental sodium; Pentothal) are an anesthetic
- Short-acting: Short-acting barbiturates (Secobarbital; Seconal), pentobarbital (Nembutal) induce sleep
- Intermediate-acting: Intermediate-acting barbiturates (amobarbital; Amytal), aprobarbital (Alurate) and butabarbital (Butisol)) induce longer sleep periods
- Long-acting: Long-acting barbiturates (phenobarbital and mephobarbital) control epileptic seizures
Give 4 ex of barbiturates and their duration of action.
- Phenobarbital (Luminal)—long- acting/1–2 days.
- Pentobarbital (Nembutal)—short- acting/2–8 hours.
- Amobarbital (Amytal)—short-acting
- Thiopental (Pentothal)—ultra–short-acting/10–20 minutes.
Barbiturates
How do these drugs work?
Like benzodiazepines, barbiturates increase the duration of GABA action on Cl– entry into the cell, which results in membrane hyperpolarization and a decrease in neuron excitability.
Barbiturates do not bind to benzodiazepine receptors.
What are the therapeutic indications for barbiturate administration?
- Induction of anesthesia—thiopental
- Anticonvulsants—eg: phenobarbital
- TX of Anxiety—rarely
- Induction of Hypnosis
Why are benzodiazepines favored over barbiturates for the treatment of anxiety?
Benzodiazepines have a much higher therapeutic index, cause less physiological dependence, and do not induce hepatic enzymes
By what routes can barbiturates be administered?
IV, PO, or IM
What are the pharmacokinetic properties of barbiturates?
They are metabolized in the liver and excreted in the urine.
What determines the duration of action of thiopental?
Redistribution to the other tissues
Does barbiturate dependency occur?
Yes. Abrupt cessation can lead to severe withdrawal symptoms (tremor, restlessness, nausea, seizures, and cardiac arrest).
For whom are barbiturates contraindicated?
For patients who have acute intermittent porphyria, because they increase porphyrin synthesis
Acute intermittent porphyria (AIP) is one of the porphyrias, a group of hereditary diseases that involve defects in heme metabolism and result in excessive secretion of porphyrins and porphyrin precursors.
-AIP manifests as episodes of abdominal pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash
What are the adverse effects of Barbituates drugs?
- -Drowsiness* and decreased motor control
- Induction of the P-450 system, which can therefore decrease the effect of other drugs metabolized by these enzymes
- -*Addiction-
In high doses, respiratory depression and coma
-Allergic reactions-
especially in patients with asthma
SEDATIVE-HYPNOTIC: BARBITURATES and Others
USE:
Treat insomnia; use for sedation, preoperative medication, barbiturate
coma (for controlled increased intracranial pressure)
SEDATIVE-HYPNOTIC: BARBITURATES and Others
Example:
pentobarbital sodium (Nembutal Sodium)
-short-acting barbiturate
SEDATIVE-HYPNOTIC: BARBITURATES and Others
How it works:
• Depression of the CNS, including the motor and sensory activities
SEDATIVE-HYPNOTIC: BARBITURATES and Others
Adult Dose:
- PO 20–30 mg TID
- Hypnotic: PO 100–200 mg
- Preoperative PO/IM/IV: 100 mg, repeat if needed
SEDATIVE-HYPNOTIC: BARBITURATES and Others
Administration:
- IV pentobarbital at a rate of less than 50 mg/min. • Do NOT mix with other medications.
- IM should be given into a large muscle.
- PO give 30 minutes before bedtime
SEDATIVE-HYPNOTIC: BARBITURATES and Others
After administrations: Safety steps
• Maintain a safe environment after administration (side rails up; proper lighting; toileting before medicating).
- Monitor vital signs.
- Observe for adverse reactions.
- Observe for signs of withdrawal if taken over a prolonged period of time and then abruptly discontinued.
SEDATIVE-HYPNOTIC: BARBITURATES and Others
Contraindications
• Respiration depression, severe liver disease, pregnancy (fetal immaturity), nephrosis
Nephrosis: kidney disease, especially when characterized by edema and the loss of protein from the plasma into the urine due to increased glomerular permeability. Also called nephrotic syndrome.
SEDATIVE-HYPNOTIC: BARBITURATES and Other
Side Effects-Adverse Reactions
SE• Nausea, vomiting, diarrhea, lethargy, drowsiness, hangover, dizziness, rash
• Drug dependence or tolerance, urticaria (hives), hypotension if given rapidly IV
AE• Respiratory distress, laryngospasm
SEDATIVE-HYPNOTIC: BARBITURATES and Other
Short Acting EX:
- Class:
- Use:
- ROA:
Secobarbital sodium
- (Seconal Sodium) class II
- Preoperative sedation / Used to induce sleep
- PO 100–200 mg before surgery / hypnotic PO/IM 100–200 mg
SEDATIVE-HYPNOTIC: BARBITURATES and Other
Intermediate-acting: Name Ex
Class:
Use:
ROA:
Amobarbital sodium
Class: (Amytal Sodium)
Use: Sleep sustainers
ROA:
Status epilepticus: IV; 5.5 mg/kg; reappear in 3–4 hours; with spinal anesthesia IV; 50–100 mg.; infused over 30 seconds; maximum dose of 250/mg
PB 50%–60%; half-life 20–40 hours;
Sedative: PO 30–50 mg BID-TID;
Hypnotic PO/IM 65–200 mg/h, IV: 65–200 mg
SEDATIVE-HYPNOTIC: BARBITURATES and Other
Provide 2 Examples of other Barbiturates
1. Chloral hydrate Class IV
2. Paraldehyde Class IV
Chloral hydrate Class IV
Describe
- -No hangover* and less respiratory depression;
- give with meals or fluids to prevent gastric irritation
Paraldehyde Class IV
Describe:
Exhaled via the lungs; strong odor and disagreeable taste; seldom used; has been used to control delirium tremens (DTS) in alcoholics; can be used for drug poisoning
