Anti-anxiety/Sedatives/Hypnotics Flashcards
General Definitions of Sedative, Hypnotic, Anxiolytic
Sedative: Calm down, treat agitation
Hypnotic: Induce sleep go to sleep fast, feel refreshed tomorrow !!!
Anxiolytic: Reduce anxiety physical, emotional, cognitive
Historical Background
Alcohol is oldest of sedative-hypnotic agents
Opium alkaloids (morphine) also used to induce stupor and sleep
In 1912, phenobarbital was the first of sedative drugs classified as barbiturates
Between 1912 and 1950, fifty barbiturates marketed commercially Barbiturates are used to relieve stress, anxiety, and to induce sleep
Sites and Mechanisms of Action
- Barbiturates reduce electrical and metabolic activity of the brain
- Accompanied by decreases in whole brain glucose metabolism
- Reductions follow reduction in excitatory activity (glutamate) or augmentation in inhibitory activity (GABA)
Sites of Action
-Amnesic properties of sedative drugs result from glutamate antagonism -
Sedative-hypnotic effect results from augmentation of GABA neurotransmission
- Barbiturates bind to specific sites on GABAa receptor
- Plays a major role in anesthetic properties of these agents
Names of Barbiturates
Amobarbital
Butabarbital
Pentobarbital
Phenobarbital
Secobarbital
Uses of Barbiturates
Barbiturate use has declined rapidly in recent years for several reasons: They are lethal in overdose
They have a narrow therapeutic to toxic range
High potential for inducing tolerance, dependence, and abuse Interact dangerously with other drugs (especially alcohol)
Not used for anxiety or insomnia
Despite the disadvantages, barbiturates are still useful
Used as anticonvulsants (for epilepsy) Used as intravenous anesthetics
Pharmacokinetics of Barbiturates
- Barbiturates are classified by their pharmacokinetics
- Short half-lives (thiopental has 3 minute redistribution half-life)
- Longer half-lives (48 hour elimination half-life for pentobarbital)
- Very long half lives (24-120 hour elimination half-life for phenobarbital)
Pharmacological Effects Of Barbs
Barbiturates have low degree of selectivity and therapeutic index
Barbiturates are not analgesic; they cannot be relied upon to produce sedation or sleep in the presence of even moderate pain
Barbiturates suppresses REM sleep, and therefore dreaming Barbiturates are cognitive inhibitors
Depress memory function, cognitive function, motor skills, and judgment
Behavior may persist for hours or days until barbiturate is completely metabolized and eliminated
Overdoses or in combination with alcohol can result in death
Barbiturate-alcohol combinations have been responsible for accidental and intentional suicides
Barbiturates in the liver stimulate synthesis of enzymes that metabolize barbiturates This produces significant tolerance
Adverse of Barbs
Drowsiness is the primary effect produced by barbiturates Impaired driving skills, judgment , and memory during period of intoxication
No specific antidotes
Treatment of overdose is aimed at supporting respiratory and cardiovascular system until drug is eliminated
Tolerance and Dependence
Barbiturates induce tolerance by either of these mechanisms:
- Induction of drug metabolizing enzymes in the liver
- Adaptation of neurons in the brain to the presence of the drug Withdraw from barbiturates results in hallucinations, restlessness, and disorientation
Names of Benzodiazepines
Sedative-Hypnotic
- Estazolam (ProSom)
- Flurazepam (Dalmane)
- Temazepam (Restoril)
- Triazolam (Halcion)
Antianxiety Alprazolam (Xanax)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Lorazepam (Ativan)
- Oxazepam (Serax)
Benzo Mech of Action
BDZ receptor linked to GABA-A receptor complex (bound to Cl channels).
BDZ enhance GABA effect GABA: an inhibitory neurotransmitter Open Cl channels in response to GABA activation, hyperpolarization, decrease neuronal firing Effects: Sedative, Hypnotic, Anticonvulsant, Muscle-Relaxant
Benzo Pharmacokinetics
Lipid-soluble: fast cross blood-brain-barrier: rapid onset of action.
Persist longer in high fat-to-lean body mass obese, elderly Abuse liability (Valium)
Benzo Adverse Effects
BZD vs other psychotropics have few SE Sedation, CNS Depression
Worse if combined with EtOH
Behavioral Disinhibition Irritability, excitement, aggression (<1%), rage
Psychomotor & Cognitive Impairment Coordination, attention (driving)
Poor visual-spatial ability (not aware of it) Ataxia, confusion
Overdose: Rare fatalities if BZD alone Severe CNS & Respiratory Depression if combined with: alcohol barbiturates narcotics tricyclic antidepressants
Benzo Dependence & Withdrawal
Except diazepam, low abuse potential if properly prescribed and supervised
Alprazolam & Triazolam low street value due to sedation lipophilic, abuse potential
Short t1/2 more intense withdrawal
