Sedatives and Hypnotics Flashcards
what are the two prominent classes of drugs classified as sedative-hypnotics?
Benzodiazepine’s
Barbiturates
what is the arousal scale for BARBs and BZDs?
- BARBs extend into the anesthesia-coma-death end (narrow TI)
- BZDs only extent into the sedation and sleep portion making them safer and more widely used
where do benzodiazepine’s and Barbiturate’s bind?
GABA A receptor-ion channel complex found in the brain and allows chloride ions (Cl⁻) to enter the cell, which inhibits nerve activity
what are the three classes of GABA receptors?
GABA a, GABA b, GABA c
what two molecules block GABAs actions?
bicuculline: interferes with GABA binding
picrotoxin: blocks chloride channel
what are the agonists for benzodiazepine receptor?
triazolam
diazepam
what are the antagonists for benzodiazepine receptor?
flumazenil
diazepam binding inhibitor (DBI): endogenous peptide
what are the inverse agonists for benzodiazepine receptor?
beta-carbolines
what are beta-carbolines?
natural product of serotonin breakdown that oppose the calming effects of benzodiazepines and a natural anxiety-promoting substance
what are benzodiazepine’s used to treat?
anxiety
epilepsy
sedative-hypnotic needs
where is the most likely site for sedation and hypnotic action in the brain for benzodiazepine’s?
in the brainstem; reticular activating system
what is the mechanism of action for the benzodiazepine’s ?
- bind at different sites
- increase the frequency of chloride channel opening
- boost GABA effect (IPSP)
- enhance GABA action
- rely on the presence of GABA (do not mimic)
what are the adverse effects of the benzodiazepine’s?
- have active metabolites
- produce severe depression when combined with other drugs
- retrograde amnesia
- motor incoordination and ataxia
what are the general effects of the benzodiazepines?
- minimal effect on respiration, cardiovascular system and GI system
- lower abuse potentials than barbs
- do not accelerate metabolism of other drugs
what is the mechanism of action for the Barbiturate’s ?
- bind at different sites
- increase duration of chloride channel openings
- increases duration of GABA effect (IPSP)
- release/block the reuptake of GABA
- GABA mimetic at high concentrations
what are the adverse effects of the Barbiturates?
- produce anesthesia, coma and death
- severe CNS depression when used with other depressants (alcohol, antihist, BZD)
- induce liver microsomal enzymes (CYP P450)
what are the general effects of Barbiturates ?
- do not have active metabolites
- less selective CNS depression: affects excitatory synapses, cell membranes, GABA receptors
- minimal cardiovascular effects
what drugs do Barbiturates increase the metabolism of?
anticoagulants
contraceptives
phenytoin
vitamin D
vitamin K
corticosteroids
what are the clinical uses for benzodiazepines?
- sedative hypnotics
- anti-anxiety
- anti-epileptic
- anti-depressant
- anesthetic adjunct
what are the clinical uses for barbiturates ?
- anti-epileptic
- cerebral edema
- short acting anesthetic
list the benzodiazepine’s
triazolam
oxazepam
chlordiazepoxide
temazepam
lorazepam
nitrazipam
diazepam
flurazepam
list the barbiturates
methohexital
thiopental
pentobarbital
secobarbital
amobarbital
phenobarbital
Alcohol is a CNS depressant that shares many pharmacologic properties with
the nonbenzodiazepine sedative hypnotics
how is alcohol absorbed?
rapidly through the stomach, large and small intestines and the colon (30-90 min following ingestion)
how is alcohol distributed?
somewhat uniform but both the placenta and BBB are very permeable to alcohol
how is alcohol metabolized?
90-98% is oxidized to carbon dioxide and water through alcohol dehydrogenase or aldehyde dehydrogenase pathway
what are the three conditions that effect the rate of alcohol metabolism?
- body weight
- drinking habits
- genetics
what is the Microsomal Ethanol Oxidizing System?
alternative pathway for metabolizing ethanol (alcohol) in the liver that uses NADPH, especially important when large amounts of alcohol are consumed or in cases of chronic alcohol use
why is alcohol metabolism accelerated when taking barbiturates?
MEOS is induced by barbs
what acute CNS effects does alcohol have on the body?
- disruption of mood, thought, memory or function
- effects sensory and motor systems
- acts as sedative hypnotic
- enhances GABA, acetylcholine and serotinergic transmitter systems
- inhibits glutamate
what cardiovascular effects does alcohol have on the body?
cutaneous vasodilation
what GI tract effects does alcohol have on the body?
- gastric acid secretion is increased
- direct irritant to gastric mucosa
- increased GI bleeding
what liver effects does alcohol have on the body?
- fat production increases
- protein accumulation
- cirrhosis/liver failure
what are the drug interactions of alcohol and aspirin?
- anti-platelet action can cause increased GI bleeding
- alcohol inhibits platelet aggregation
what are the drug interactions for alcohol and oral hypoglycemics ?
alcohol inhibits the metabolism of oral hypoglycemics (tolbutamide) taken by diabetics which causes stronger reduction of blood glucose due to alcohols effect of decreasing blood glucose levels
what is the function of Tolbutamide ?
stimulates insulin release
what are the characteristics of chronic alcoholism?
- weight loss, nutritional deficiencies, vitamin deficiencies
- liver cirrhosis
- GI irritant
- Wernicke’s Encephalopathy
- personality changes
- Korsakoff’s psychosis
- delirium treatments
- heart failure
Disulfiram (Antabuse)
Inhibits Aldehyde Dehydrogenase (ALDH) which leads to accumulation of acetaldehyde when alcohol is consumed — so it’s used as a negative reinforcement tool in treating alcohol dependence
Naltrexone (ReVia)
opioid receptor antagonist that blocks the brain’s opioid receptors, which are involved in the reward and pleasure pathway triggered by alcohol
Acamprosate (Campral)
blocks NMDA (glutamate) receptors, helping to regulate excitatory neurotransmission to restore chemical balance in the brain disrupted by chronic alcohol use
what are the types of insomnia?
transient
short term
long term
Transient Insomnia
triggered by minor, temporary stressors like upcoming exams, travel (jet lag), change in schedule or drug-induced (e.g., caffeine, stimulants) but typically resolves on its own once the trigger is gone
short term insomnia
Lasts a few weeks, caused by more significant stress or life events like job loss, grief, relationship issues and more persistent than transient
long term insomnia
Persists for months or longer, often has no clear or immediate cause but could be related to underlying psychiatric conditions
A good anti-insomnia drug should:
Reduce sleep latency
Increase total sleep time
what are the 5 stages of sleep?
Stage 1: Light sleep — transition from wakefulness
Stage 2: Slightly deeper sleep — still light
Stage 3: Beginning of deep sleep (slow-wave sleep)
Stage 4: Deepest non-REM sleep — important for physical restoration
Stage 5: REM (Rapid Eye Movement) sleep — dreaming happens here, also called paradoxical sleep because the brain is active but the body is relaxed
what are the time frames of drug prescriptions for insomnia?
transient: small dose for 1-3 nights
short term: small dose for 2-3 weeks
long term: longer period of time but not exceeding 1 month
what are the commonly used hypnotics (BZDs)?
Triazolam (Halcion)
Oxazepam (Serax)
Temazepam (Restoril)
Flurazepam (Dalmane)
what are other commonly used hypnotic agents?
Zolpidem (Ambien)
Eszopiclone* (Lunesta)
Amitriptyline
Anti-histaminics (H1)
Alcohol (ethanol)
Melatonin
Triazolam (Halcion)
- short half-life; rapidly absorbed and eliminated (no morning left over sedation)
- useful in the elderly (reduced drug metabolism)
- more lipid soluble than oxazepam
- less of a change in sleep patterns (REM and Stage 4) than flurazepam
- recommended for use up to 42 days
- rebound daytime anxiety and confusion
Oxazepam (Serax)
- short half life; slow onset of action
- low lipid solubility/slow penetration into the brain
Temazepam (Restoril)
intermediate acting benzodiazepine
Flurazepam (Dalmane)
- decreases REM and sleep stage 3 & 4
- long duration of action
- short term 14-28 days
- morning-after-sedation-hangover effect due to the long half-life of this drug
- problematic use in the elderly
Zolpidem (Ambien)
- binds to benzodiazepine receptor
- is structurally unrelated to the benzodiazepines
- has only minor effects on sleep stages
- has no anxiolytic, anticonvulsant or muscle relaxant properties
- peak activity in 1~2 hrs. (half life = 2.5 hrs)
- as effective as a benzodiazepine for inducing sleep
Eszopiclone* (Lunesta)
- binds to benzodiazepine receptor
- is structurally unrelated to the benzodiazepines
- has no anxiolytic properties
- peak activity in 1hr (half life = 6 hrs)
- as effective as a benzodiazepine for inducing sleep
- The only hypnotic FDA approved for a long-term use (more than 42 days)
Amitriptyline
a sedative and an antidepressant blocks the reuptake of 2 neurotransmitters (serotonin (5-HT) and norepinephrine)
Anti-histaminics (H1)
over-the-counter preparations cold remedies/anti-vertigo (seasickness), anti-allergic medications.
