Pharm - Sedative Hypnotics

Depressants

What are sedative-hypnotics also called?

Slow it down

What do sedative-hypnotics do to brain activity?

Sedation, hypnosis, anxiety relief

What are the three main effects of sedative-hypnotics?

A drug that produces a calming effect

What is a sedative drug?

Relaxation and reduced anxiety

What does a sedative encourage?

Muscle relaxation

What additional effect can sedatives have on muscles?

A drug that produces drowsiness

What is a hypnotic drug?

Fall asleep and maintain sleep

What do hypnotics help patients do?

It is markedly reduced

What happens to CNS function with hypnotic effects?

Dose

What determines whether a drug produces sedation or hypnosis?

Dose-response relationship

The relationship between drug dose and effect is called the ______.

Benzodiazepines, Z-drugs, buspirone, barbiturates

What are the four classes of sedative-hypnotics?

Benzodiazepines

Which sedative-hypnotic class is most commonly used clinically?

Insomnia

What are Z-drugs primarily used to treat?

Adverse drug reactions

Why are barbiturates least commonly used?

Seizures and anesthesia

What are barbiturates still occasionally used for?

Alprazolam, clonazepam, lorazepam

Which benzodiazepines are used for panic disorder?

Benzodiazepines

What medication classes are used for generalized anxiety disorder?

Estazolam, flurazepam, temazepam, triazolam

What benzodiazepines are used for insomnia?

Diazepam, lorazepam

Which benzodiazepines are used for seizures?

Diazepam, chlordiazepoxide, lorazepam

Which benzodiazepines are used for alcohol withdrawal?

Diazepam, clonazepam

Which benzodiazepines can treat muscle spasms?

Benzodiazepines

Which sedative-hypnotic class is most commonly prescribed?

Alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, temazepam, triazolam

What are the 12 benzodiazepines listed in the lecture?

Xanax

What is the brand name for alprazolam?

Klonopin

What is the brand name for clonazepam?

Valium

What is the brand name for diazepam?

Ativan

What is the brand name for lorazepam?

Librium

What is the brand name for chlordiazepoxide?

Schedule IV

What controlled substance schedule are benzodiazepines?

Controlled substance with low abuse and dependence risk

What does Schedule IV indicate?

DEA number

What is required to prescribe benzodiazepines?

GABA

What neurotransmitter do benzodiazepines enhance?

Gamma-aminobutyric acid

What does GABA stand for?

Slows brain activity

What is GABA's main function?

Inhibits neuronal activity

How does GABA affect CNS signaling?

Sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxing

What are the five major effects of GABA enhancement?

GABA-A

What receptor do benzodiazepines act on?

Ligand-gated ion channel

What type of receptor is GABA-A?

G protein-coupled receptor

What type of receptor is GABA-B?

Chloride (Cl-)

What ion enters neurons when GABA-A channels open?

The neuron becomes less excitable

What happens when chloride enters a neuron?

Norepinephrine, acetylcholine, serotonin, dopamine

GABA reduces neuronal responsiveness to which neurotransmitters?

Variations in receptor structure across brain regions

Why do individual benzodiazepines have different effects?

Oral and IV

What pharmacokinetic routes allow rapid benzodiazepine absorption?

No; slow and unpredictable

Is IM benzodiazepine absorption reliable?

Clorazepate

Which benzodiazepine is a prodrug?

48 hours

What is the half-life of clorazepate?

Long half-life

Why is clorazepate useful for alcohol withdrawal and seizures?

80–98%

What percentage of benzodiazepines are bound to plasma proteins?

Yes

Are benzodiazepines lipid soluble?

Cross the blood-brain barrier quickly

What does high lipid solubility allow benzodiazepines to do?

Lipophilicity

What influences benzodiazepine duration of effect?

Diazepam and midazolam

Which benzodiazepines are the most lipophilic?

Diazepam and midazolam

Which benzodiazepines have the fastest onset?

CYP450 and glucuronidation

What are the two main liver metabolic pathways for benzodiazepines?

CYP450

Which pathway metabolizes most benzodiazepines?

Active metabolites

What can CYP450 metabolism produce?

Chlordiazepoxide, diazepam, flurazepam, clonazepam, clorazepate

Which benzodiazepines are long-acting according to the lecture?

Over 100 hours

How long can some active benzodiazepine metabolites have a half-life?

Daytime sedation

What unwanted effect can long-acting metabolites cause?

Lorazepam, oxazepam, temazepam

Which three benzodiazepines are metabolized by glucuronidation?

LOT

What is the memory aid for benzodiazepines metabolized by glucuronidation?

No

Does glucuronidation produce active metabolites?

Shorter

What is the duration of effect of LOT benzodiazepines?

LOT

Which benzodiazepines are preferred in elderly patients?

Kidneys

How are benzodiazepines and their metabolites primarily excreted?

Increases

What happens to benzodiazepine half-life in older adults?

Increases

What happens to benzodiazepine half-life with renal dysfunction?

Clorazepate, chlordiazepoxide, clonazepam, diazepam, flurazepam

Which benzodiazepines should be avoided in renal insufficiency and ESRD due to active metabolites?

Drowsiness, dizziness, decreased alertness, impaired concentration

What are common benzodiazepine adverse effects?

Impaired driving

What driving-related effect can benzodiazepines cause?

Decreased libido and erectile dysfunction

What sexual adverse effects can benzodiazepines cause?

Hypotension

What cardiovascular adverse effect can benzodiazepines cause?

Use the smallest effective dose

What is the main goal when using benzodiazepines for sedation?

Decreases

What happens to mental alertness with benzodiazepine sedation?

Decreases

What happens to coordination with benzodiazepine sedation?

Time required to fall asleep

What is sleep latency?

Decrease it

How do benzodiazepines affect sleep latency?

Stage 1

Which sleep stage is the lightest non-REM sleep?

Stage 2

Which sleep stage accounts for approximately 45% of sleep?

Stage 3

Which sleep stage is the deepest non-REM sleep?

REM (Stage 4, per lecture)

Which sleep stage is associated with dreaming?

Stage 3

Which sleep stage is needed to feel rested?

Increase duration

How do benzodiazepines affect stage 2 sleep?

Decrease duration

How do benzodiazepines affect stages 1, 3, and 4?

No

Do benzodiazepines provide pain relief?

No

Do benzodiazepines block pain receptors?

Premedication, sedation, induction

What are benzodiazepines used for in general anesthesia?

Reduce abnormal electrical activity

How do benzodiazepines help with seizures?

Prevent and stop seizures

What is the anticonvulsant effect of benzodiazepines?

Muscle relaxation

What additional effect can benzodiazepines have on skeletal muscles?

MG, OSA, chronic bronchitis, COPD

Which patients are at increased risk of respiratory depression from benzodiazepines?

Pulmonary disease and sleep apnea

Which respiratory conditions require caution with benzodiazepines?

Reduced cardiac contractility

What cardiovascular effect can occur when benzodiazepines accumulate to toxic levels?

Decreased response after prolonged use

What is benzodiazepine tolerance?

GABA-A receptors become less responsive

Why does tolerance develop?

Increased dose or frequency

How may tolerance affect a patient's medication use?

Yes

Does benzodiazepine tolerance cross over to other sedatives?

Alcohol, Z-drugs, barbiturates

What substances can demonstrate cross-tolerance with benzodiazepines?