Anxiolytics Flashcards
Anxiolytic
A drug that reduces anxiety without causing significant sedation
Depressant
General term for any drug that slows or reduces CNS activity, drugs can belong to different pharmacologic classes
Sedative
Drug used to relax, calm, or tranquilize
Hypnotic
Drug used to induce sleep
Barbiturate
Class of prescription drugs used to sedate, reduce anxiety and general anesthesia
Benzodiazepine
Class of prescription drugs used to sedate, reduce anxiety and reduce muscle tension
Non-barbiturate/Non-benzodiazepine
Prescription drugs from different classes used to sedate, promote sleep and reduce anxiety
Inhalants
Chemicals that depress CNS function via inhalation, many are household products
Barbiturate
High potential for abuse/dependence
Often paired with anphetamines in 1940s
Low therapeutic index
Several still in use today
Onset and Duration Barbiturate
Ultra Short(Methohexital) .2 min onset, .25 hour duration
Short(pentobarbital) 15 minute onset, 2-3 hours
Medium (Aprobarbital) 30 minute onset, 5-6 hour duration
Long, (mephobarbital) 60 minute onset, 6-10 hour duration
Mechanism of Action
Potentiate the effects of neurotransmitter GABA
Enhance binding to GABA receptor
Barbiturate binding sites are near GABA binding sites
Inhibits release of excitatory neurotransmitter
Higher doses mimic the effects of GABA
Lead to profound CNS depression and reduced respiration
Paradoxical stimulation of CNS at low doses due to suppression of inhibitory brain systems
Barbiturate Effect on CNS
Low dose: euphoria, sense of well being, greater self esteem, increased feelings of confidence, increased talking and social acceptability
Moderate Dose: Sedation and sleep
Higher Dose: Surgical Anesthesia
Overdose: Coma
Barbiturate Pattern of Use and Abuse (General)
Oral administration most common route
Pentobarbital (yellow) and secobarbital(red) are preferred
Older adults
Original contact may be via prescription for insomnia or anxiety
Patterns range from infrequent sprees of gross intoxication lasting a few days to prolonged compulsive daily use
- Hover around 19% of population
- Taken by opiate dependent individuals trying to boost heroine- use frequent enough to develop tolerance to both drugs which complicates treatment
Alcoholics use it to relieve from withdrawal
Barbiturate Use and Abuse Types
Adults
Obtain prescription for anxiety or insomnia
Develop tolerance, get higher dose–> physical dependence
Get prescription from multiple physicians to hide abuse
don’t refer to themselves as abusers
Young Adults
Diverted prescription meds to get high
Typically take at large doses with ethanol
Thriving black market
Frequency of use is episodic, so dependence does not always occur
Acute toxic reactions are frequent
Metabolic Tolerance- Barbiturate
Increase liver enzymes that metabolize barbiturates, shortens duration but does not induce need for higher doses
Pharmacologic Tolerance- Barbiturate
Reduced sensitivity to direct effects on neurons resulting in lowered CNS, respiratory and toxic effects, dose must be increased to achieve original response
Cross Tolerance- Barbiturate
Tolerance to lethal effects does not occur
Cross tolerance is complete with many CNS depressants, including alcohol
Dependence- Barbiturate
Like alcohol
Onset of withdrawal depends on half-life
Tremors, hallucinations, convulsions, delirium
Withdrawal can be fatal
Benzodiazepine Clinical Use
Anxiety Disorder GAD, acute anxiety, panic disorder, social phobia, PTSD, OCD Anxiety Illness cardiovascular, GI, chemotherapy Insomnia Convulsive, spastic, involuntary movement Detoxification Pre-surgical anesthetic
Benzodiazepine Half Lives
Anxiolytics Clorazepate- 2 Oxazepam- 8 Chlordiazepoxide-10 Alprazolam- 12 halazepam- 14
Anticonvulsant
clonazepam- 23
Hypnotic midazolam-2 triazolam- 3 estazolm- 10 temazepam- 11
Preanesthetic
midazolam-3
Benzodiazepine Mechanism of Action
Potentiate the effects of GABA
Binding sites near GABA binding sites
Self-limiting effect, so toxicity is low
Affect neurons at all levels, including CNS and muscles
Increases the flow of Cl- ions into the cell
Benzo effect at different doses
Low- Reduces anxiety, not general depressant
Moderate- Light headedness, lassitude, increased reaction time, sedation
High- Motor incoordination, relaxed muscle tone, impaired mental function, confusion, sleep
Higher- anteretrograde, amnesia
Benzo Use and Abuse
Similar to barbiturate
Only short acting alprazolam and highly lipophilic diazepam are abused
Taken with other drugs
Take the edge of the fear of trying other drugs
Animal models- Barbiturates more self administered than benzos
Most commonly mentioned in combination with another drug
Perceived as reinforcing, but generally only by experienced sedative users/abusers
naive subjects don’t like the effects
Schedule IV
Benzo Tolerance
Similar to barbiturate, except benzo does not stimulate its own metabolism
Develops to all CNS effects except to memory disturbances
Tolerance to sedative effects quickly
Benzo Dependence
Similar to benzo but less severe
Convulsions can occur, but are rare
Withdrawal symptoms– similar to anxiety so difficult to document
Receptor antagonist can precipitate withdrawal
Anxiety
Cardinal symptom of many psychiatric disorders, but frequent component of medical/surgical procedures
Emotion that allied with fear is adaptive
Separate acute episode-dependent anxiety from non specific disease-driven anxiety, drugs better at treating the former
Treatment should be limited in duration
Insomnia
Treated carelessly
Prescribing drugs without knowing what causing the insomnia puts patient at risk for abuse
Behavioral therapy, psychotherapy or nonhypnotic drugs may be superior to hypnotics when there is a specific cause
If transient in nature, use may be satisfied
- Administer no more than every third night to avoid abuse
Other Insomnia Agents
Ambien, Sonata and Lunesta
Non benzo used for short term management for insomnia
Little occurrence of tolerance or rebound insomnia
Schedule IV
Inhalants: Definition and Type
Breathing in chemical vapors to get high
Common Home or Workplace Products
Adhesive, Aerosols, Anesthetics, Cleaning Agents, Volatile Solvents and gases, erosol whipped cream canisters, room deodorizers
Volatile Solvents
Gases or liquids that vaporize at room temperature
ex. paint thinners, nail polish removers, degreasers, felt tip markers, adhesives, glue
Aerosols
Sprays that contain solvents and propellants
spray paint, hair spray deodorant spray, fabric protector spray
Gases
Found in household/commercial products as well as anesthetics
ex. butane lighters, propane tanks, refrigerant gases, ether, chloroform, halothane
Nitriles
Special class used primarily as sexual enhancers ex. Vasodilators, smooth muscle relaant Amyl nitrile packaged in ampules commonly known as "poppers" and are highly flammable Butyl nitrite found in video head cleaner, room odorizer, leather cleaner
Scope fo Abuse
Primarily abused by boys 10-15
adolescents between 12-17
Adults exposed at work place can also abuse
Abuse increasing, especially among isolated Native American and Hispanic populations
Products readily available and inexpensive
Other countries now experiencing problems
Most tried drug of abuse in 8th grade
Inhalant Use
Directly from container to nose
From a soaked rag through the mouth
From a soaked bag
From inside a balloon
Inhalation continues until desired effects, few minutes
Leads to unconsciousness, relax grip on bag, and let fall away so that individual breaths again
Both solo and group sniffing bags, bags are sometimes shared
Pattern of Abuse- Inhalant
Typically episodic in nature following fads
“Huffing”- through mouth
“Sniffing” through nose
Semiliquid products placed in bags and held over mouth and nose,
Heating increases the concentration
Gas sprayed onto cloths , propellants separated from particulates
Access of Inhalant
- Products are widely available, accessible, inexpensive to use and legal
Warning labels alert individuals to potentially new sources
Isolated pockets of abuse can grow quickly if overreact in the media
Inhalant Pharmacology
General CNS depressant, but can stimulate at low doses
Onset of action and duration of action typically short
Effects- Inhalant
Immediate effects are euphoria, giddiness,, ataxia, slurred speech, perceptual distortions
Effects last 15-45 minutes after sniffing ends
Drowsiness and stupor last for 1-2 hrs
Tolerance- Inhalant
Many anecdotal reports exist
Unknown if cross tolerance exists
Dependence Inhalant
No evidence for physical dependence,
unlikely because short duration of action
- If exists, similar to barbiturates and ethanol
Treatment for Abuse
No accepted treatment plan
Many centers refuse to treat because believe that abusers are resistant to treatment
Complex psychosocial, economic and biophysical issue, longer time periods are needed for treatment
- No support from insurance for treatment
Nitrous Oxide
Lauging gas
Colorless, non-flammable gas with slight sweet odor
Currently used in surgical procedures as well as minor dental procedures
Thought of as a minor anesthetic
reports of use on a small scale since 1971
Most used by inhaling from balloons or plastic bags
Generally pleasant effects, but short lived
Cognitive deficiencies were noted during high
Nitrous Oxide- Mechanism of Action
Not completely understood
Most likely modulates ion channels
Blocks NMDA and acetylcholine regulated channels
May inhibit GABAc and 5-HT receptors
May slightly potentiate GABAa and glycine receptors
Anxiolytic effect- GABA a
Analgesic Effect- endogenous opioids and noradrenergic
Euphoria- mesolimbic pathway via antagonizing NMDA receptors that hten increase dopamine release in ventral tegmentum and nucleus accumbens
Nitrous Oxide Time Course
Effects perceived at 10% concentration Deprives brain of oxygen At 100%, experience sense of well-being, "high" Difficultly maintaining balance Slow to answer questions Low response to pain, noise and speech Lapse into unconsciousness Breathing reflex is surppressed for a few seconds Can be fatal very quickly
Nitrous Oxide Methods
Crackers: 2’ metal or plastic cannisters filled with pure N2O
Whip Its: Small cartridges used for dispensing whipped cream, discharged into a balloon and then inhaled
Tanks; Either medical grade or autoracing grade tanks, 20 pounds
Charging Bottles: similar to seltzer bottles
Nitrous Oxide- Long Term Toxicity
Nitrous oxide binds with oxygen in body Results in vitamin B12 deficiency RBC count is lowered anemia Nerve degeneration can occur, results in pain in arms and legs, unsteady gait, irritable, cognitive deterioration Severe headaches Rashes in nose and mouth Weight loss Red eyes, glassy eyes Menstrual disorders Night sweats
Inhalant Effects on Brain
Atrophy of cerebral, cerebellar and brainstem white matter, resulting in dementia
Chronic use can lead to neuropsych deficits, such as impairments in processing speed, attention, memory retrieval, language and executive function
Consisten with white matter pathology
Sudden Sniffing Death Syndrome
Most common form of acute death
Can occur after only 1 use
Precipitated when startled- causes a burst of epinephrine that can cause fatal cardiac arrythmia
Death by aspiration, accidental trauma while under the influence, or suffocation
