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Pharmacology Test 4 > Chapter 22: Sedative Hypnotics > Flashcards

Chapter 22: Sedative Hypnotics Flashcards

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1
Q

What is a sedative-hypnotic?

A

These medications will cause sedation.
Have a calming effect, relief of anxiety.
Encourage sleep (hypnotic)
Widely prescribed world-wide.

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2
Q

What are the classifications of sedative-hypnotics?

A
  1. Benzodiazepines - Diazepam, Midazolam
  2. Barbiturates - Phenobarbital
  3. Sleep Aids - Zolpidem (non-benzo)
  4. Anxiolytics - Buspirone (non-hypnotic)
  5. Ethanol - Booze
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3
Q

How do sedative-hypnotics work?

A

These drugs bind to the GABA receptor and potentiate inhibition at all levels of the CNS by increasing Cl- flow through the channel (hyperpolarization) and increase opening time.

This sets up an Inhibitory Post Synapatic Potential

Some sedatives hypnotics also decrease glutamate signaling

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4
Q

What are the sedation effects of Sedative Hypnotics?

A

Calming, anxiolytic (most common)
Depressant effects on psycho-motor functions
Dose-dependent anterograde amnesia- patient will not remember what happened

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5
Q

What are the desirable hypnosis effect of Sedative Hypnotics?

Less desirable?

A

Dose dependent
Decrease time to fall asleep
Increase stage 2 NREM (non-rapid eye movement ) sleep, more restful sleep.

Less Desirable:
Decrease REM sleep
Decrease stage 4 NREM slow-wave sleep

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6
Q

How are SH used in anesthesia?

A

SH are useful as anesthesia adjuncts.

Barbiturates : Thiopental and Methohexital
Very lipid soluble, penetrate brain tissue rapidly
Short action of duration

Benzodiazepines: Diazepam, Lorazepam, Midazolam
Combined with other agents
Can cause post-anesthetic resp depression

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7
Q

What are Benzodiazepines reversed with?

A

Flumazenil, GABA antagonist

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8
Q

What are additional effects of sedative hypnotics?

A

Anti-convulsive - seizure medication (barbituates)
Muscle Relaxation - treat muscle spasms with benzos
Respiration/Cardiac Functions - comparable to natural sleep, minimal effects on cardiac activity.

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9
Q

Where is alcohol primarily metabolized?

A

90% of EtOH is metabolized in the liver.
10% of EtOH is metabolized in the lungs and stomach.

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10
Q

What are the two major pathways of metabolism of EtOH to Acetaldehyde?

A
  1. Alcohol Dehydrogenase Pathway (Liver)
  2. Microsomal Ethanol- Oxidizing System (MEOS)
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11
Q

What is the rate of oxidation for EtOH?

How fast do adults metabolize EtOH?

What is blood alcohol level is considered impaired?

What are fatal levels?

A

Zero Order Kinetics
The more you ingest, the more it raises the blood alcohol level

Adults can metabolize one standard drink an hour (7-10 grams or 150-220 mmol/hr). A beer/hour.

0.08 (impaired)

0.4 (fatal)

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12
Q

What compound is a contributing factor to hangovers and headaches form EtOH?

A

Acetaldehyde

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13
Q

What enzyme is used to break down EtOH to acetaldehyde?

What coenzyme is used in this pathway and what does it get reduced to?

A

Alcohol Dehydrogenase

NAD+ is used and is reduced to NADH

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14
Q

What does NADH do to fatty acids?

When does this become a problem?

A

NADH blocks the breakdown of fatty acids.

Increasing NADH from increasing EtOH consumption will lead to increase fatty acids in the liver leading to alcohol steatohepatitis, cirrhosis, failure of the liver.

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15
Q

What enzyme breaks down acetaldehyde?

What is the end result?

A

Aldehyde dehydrogenase

Acetate (gas that is freely blown out through the lungs)

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16
Q

What is Fomepizole used for and what does it do?

A

Used for emergency ingestion of antifreeze, ethylene glycol, methanol (suicidal attempt).

Blocks alcohol dehydrogenase so that ingested substances do not get converted to formaldehyde (very toxic).

17
Q

What is Disulfiram (antabuse) used for and what does it do?

A

Used to elevate acetaldehyde by blocking aldehyde dehydrogenase.

This is use to deter patient from drinking. (Recovering alcoholics)

18
Q

How does the Microsomal Ethanol Oxidizing system work (cytochrome P450 pathway)?

A

The NADPH coenzyme and the MEOS will convert EtOH to acetaldehyde.

19
Q

What are the changes with chronic consumption of alcohol?

Essay question

A

Tolerance: more drug is needed for same initial effect

Dependence: body is reliant on drug, if they stop taking the drug there will be SE/ withdrawal symptoms

Addiction Behavior: will seek out drug regardless of consequences (lose job, gets divorce)

20
Q

How are GABA and Glutamate affected by EtOH?

A

EtOH enhances GABA at the GABA receptors.
EtOH inhibits the ability of glutamate to open cation channels.

21
Q

What is a fatty liver with no inflammation called?

A

Steatosis

22
Q

What is the most common neurotoxicity from EtOH?

What are other neurological disorder from chronic use?

A

Generalized symmetric peripheral nerve injury, distal paresthesias of hands and feet.

Gait disturbances, ataxia
Optic nerve degeneration
Dementia, demyelinating disease

23
Q

What is the Wernicke-Korsakoff Syndrome?

A

Disorder associated with Chronic Alcohol Use:
Paralysis of the external eye muscles
Ataxia
Confusion
Psychosis, Coma, Death
Thiamine Deficiency (Banana Bag)

They are eating less regular meals and using EtOH as primary source of calories.

24
Q

What are symptoms of Alcohol Withdrawal Syndrome?

A

Motor Agitation
Anxiety
Insomnia
Reduced Seizure Threshold

25
Q

What are the levels of alcohol withdrawal syndrome?

A

Mild: 6-8 hours after consumption stops, last 1-2 days.
Tachycardia, HTN, tremors, anxiety, insomnia.

Severe: Can last 1-5 days. (can be deadly)
W/d seizures- most common cause of seizures in adults, d/t suppression of GABA receptors. Glutamate going hog wild.
Alcoholic hallucinations

Delirium Tremens (Extreme) (deadly)
Delirium, agitation, autonomic system inability, fever, diaphoresis

26
Q

What are treatments for alcohol withdrawals?

A

Naltrexone- long lasting opioid antagonist, used to treat alcohol dependence, suppresses alcohol effects, must be opioid free if starting this medication.

Acamprosate- adjunctive, normalizes brain pattern, restoring GABA receptors to normal

Disulfiram (Atabuse) (decline)- when taking alcohol
This will cause flushing, throbbing, HA, N/V, sweating, hypotension, and confusion. Blocks aldehyde dehydrogenase.

27
Q

What are non-pharmacological treatment of sleep problems?

A

Proper Exercise and Diet
Stimulant (Caffeine) avoidance
Comfortable sleep environment, routine

28
Q

What are pharmacological treatment of sleep problems?

A

OTC with antihistamines
Benzo/Barbiturates will result in less effective sleep b/c of deep stage 4 sleep.

Most common:
Zolpidem (Ambien) and Eszopiclone (Lunesta) - abuse potential. Usually 7-14 day prescription.

Pharmacology Test 4 (5 decks)

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