Depressants, Benzodiazepines, and Psychiatric Drugs: A Comprehensive Guide
Depressants
• Barbiturates
– Within the family of depressants (derived from barbituric acid)
– Used as sedative-hypnotic and antiepileptic medication
• Short-acting barbiturates (< 4 hours) – secobarbital, pentobarbital (Seconal, Nembutal)
• Intermediate (4 – 6 hours) – amobarbital (Amytal)
• Long (> 6 hours) – Mephobarbital (Mebaral), phenobarbital
• But à injection faster acting than oral administration
– Higher dose lasts longer than lower dose
• Ultra-short acting – mostly used for surgeries or emergency situations
– Little appeal as a recreational drug à not commonly abused
• In general, same effects as depressants
• Low doses (oral administration) – relaxation (and sense of euphoria)
– Disinhibition of the cerebral cortex
• Inhibitory influences from the cortex reduced
• Symptoms similar to inebriation or intoxication from low doses of alcohol
• Truth serum? Say anything serum?
• ↑ in dose levels, lower regions of the brain concerned with general arousal become affected
• 100 mg (therapeutic dose) – drowsy, sedated à Can affect performance of driving a car or operating heavy machinery
• Higher doses à hypnotic (sleep-inducing) effect
• Historically – used to treat insomnia
– Sleep induced not normal
– Suppressed REM (rapid eye movement) sleep
• REM sleep – dreaming and relaxation of the body
• If barbiturates taken then stopped, the body tries to compensate for lost REM sleep
– REM sleep rebound – longer periods of REM sleep
• Vivid upsetting nightmares à barbiturate hangover (next day)
• Groggy and “out of sorts”
• Possibility of lethal overdose
– Taking a high dose level (depends on tolerance)
– Taking with alcohol
à coma and death (excessive dose produces inhibition of the respiratory control centers in the brain)
• Alcohol + barbiturates è synergistic
• Suicidal potential à ↓ as prescription sedative
• Long-acting barbiturates
• Use as sleep medication initiates a cycle of behavior that can lead to dependence
• Even after brief use, can temporarily ↑ anxiety during the day à greater degree of insomnia than before
• Barbiturate-induced sleep à groggy the next morning à stimulant to feel alert à still feel stimulant at night à continue taking barbiturate to achieve sleep
• Tolerance
• Withdrawal symptoms à physical dependence
• Abrupt withdrawal can lead to death (closely resembles alcohol withdrawal)
• Because of problems associated with its treatment of insomnia, no longer used for this purpose
• Epileptic seizures; phenobarbital prescribed to prevent convulsions
• Dose levels need to be monitored carefully
• Concentrations high enough to control seizures without drowsiness
• Abuse potential high for short-acting barbiturates
• Positively reinforcing (rat studies, comparable to cocaine)
• Abuse peaked in the 1950s and 1960s, overshadowed by other illicit substances
• Less widely available as prescription drugs
• Stricter controls for obtaining excessive doses at pharmacies
• Doctors reluctant to prescribe due to suicide risk
Benzodiazepines
• Anti-anxiety medication
• Selective effect on anxiety
– Tranquilizing effects, rather than sedative effects
• Useful for anxiety and stress-related problems, but not the miracle drug promoted to be in the 1960’s/1970’s
• Long-acting – Valium (diazepam)
• Intermediate acting – Ativan (lorazepam), Restoril (temazepam)
• Short-acting – Xanax (alprazolam)
• Absorbed slowly into the bloodstream
– Relaxant effects develop more gradually than barbiturates à last longer
• Higher level of safety
– Respiratory centers in the brain not affected
– Rare to die of respiratory failure from overdose (intentional or accidental)
• As long as other depressant drugs not taken concurrently
• Dangers – long-acting benzodiazepines, rate of elimination slow, buildup after several doses (mostly in the elderly population)
– Drug-induced dementia in the elderly
– Long-acting benzodiazepine no longer recommended for this age group, switch to shorter-acting for anxiolytic effect
• Tolerance effects or acquired dependence
• Tolerance to the sedative effects (when taken for insomnia) – more required to induce sleep in later administrations
• Symptoms of benzodiazepine dependence:
– For slow-acting benzodiazepines withdrawal effect appear later (3-6 days)
– Anxiety level higher (worse than the original level; rebound anxiety)
– Insomnia, restlessness, agitation
– Less severe than barbiturate withdrawal
– Occur only after long-term use
– Subside in 1 – 4 weeks
In the Brain
• Heightens the effect of neurotransmitter GABA (gamma-aminobutyric acid)
• GABA exerts an inhibitory effect on the nervous system
• Greater inhibition with benzodiazepines, ↓activity level of neurons involved
• Cross-tolerance!
• Does not present the same potential for abuse as cocaine, alcohol or barbiturates
1. Weak reinforcers of behavior
– Rat studies, self-administration far less than for barbiturates
2. Slow onset of effect – no sudden “rush” felt in other drugs of abuse: cocaine, heroin, amphetamines
• Multiple substance abuse/polydrug abuse
– Alcoholics – to relax, avoid the smell of alcohol in breath
– Heroin abusers – augment euphoria, reduce anxiety when opiate levels fall
– Cocaine abusers – soften the crashing feeling when drugs wear off
• Misuse > abuse
– Most frequently prescribed and for excessive dosages
• Safe for short-term use, adverse side effects in long-term use
Rohypnol (flunitrazepam) – previously colorless, odorless, tasteless. Now turns blue when dissolved in clear liquid
Psychiatric drugs
• Used to treat mental illnesses (psychotropic)
• Schizophrenia (antipsychotic drugs) and mood disorders (depression, mania) (anti-depressants, mood stabilizers)
• Schizophrenia
– “Split-mind” – split off or broken off from a sense of reality.
– NOT multiple personality disorder (dissociative disorder)
– Delusions, leading to feelings of persecution, paranoia, auditory hallucinations – “voices”
– Not all suffer delusions, hallucinations – dulled emotions, catatonia (odd rigid, prolonged body posture)
– Early treatment: barbiturates, prefrontal lobotomies
Antipsychotic drugs
• Therapeutic medications:
• First-generation antipsychotics
– Chlorpromazine (Thorazine), haloperidol (Haldol)
– Effective in reducing symptoms for many patients
– But also carry the potential for development of severe movement-related motor problems (Parkinson’s-like symptoms)
• Second generation
– Clozapine (Clozaril), risperidone (Risperdal)
– Treat a wider spectrum of symptoms, without movement difficulties
– Clozaril – Agranulocytosis, lethal blood disease, need to monitor blood
– Risperdal – hyperglycemia, not recommended to treat psychotic symptoms related to dementia in the elderly – heart problems and respiratory infections
• Third generation
– Apiprazadole (Abilify)
– Effective treatment without risks from previous generation antispsychotics
– Modulate dopamine activity, stabilizes dopamine receptors
Antidepressants
• Major depression (severe, debilitating depression) most common form of mood disorder
• Emotional state far beyond ordinary feelings of sadness, grief or remorse
• Many depressed individuals turn to alcohol for relief
– Depressant action on the nervous system makes the condition worse
– Alcohol dependence and alcoholism
• Risk of suicide, major concern
– Attempts increased during the upswing of mood after a deep period of depression
– When depression is most intense, little energy to engage in suicidal feelings or thoughts
• First-generation antidepressants
– MAO (monoamine oxidase) inhibitors
• First group developed to treat depression
• Needed to be on a restricted diet to avoid serious adverse side effects (MAO breaks down tyramine)
– Tricyclic antidepressants
• Do not require dietary restrictions
• Effects on the cardiovascular system (elevated heart rate) make them undesirable for certain patients (cardiovascular disease)
• Second generation
– Fluoxetine (Prozac)
– Slow reuptake of serotonin
– Selective serotonin reuptake inhibitors (SSRIs)
• Third generation
– Slow reuptake of serotonin and norepinephrine in the brain
Mood Stabilizers
• Mania – as disruptive as depression
– Sleeplessness, impulsiveness, irritability, feelings of grandeur
• Bipolar disorder (manic-depression)
– Extreme mood swings back and forth between depression and mania
• Treatment
– Lithium carbonate or valproate (Depakote)
– Antipsychotic medications risperidone (Risperdal)
– Combination of antipsychotic and antidepressant medications (Symbyax)