Anxiolytic & Hypnotic Drugs

The video introduces the topic of anxiolytics and hypnotics, defining anxiety as an unpleasant sensation of fear or apprehension often accompanied by physical symptoms like tachycardia, palpitations, hypertension, tremors, and diaphoresis. It attributes anxiety to limbic system dysfunction, which is crucial for emotions and memories.

Anxiety is primarily linked to low levels of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter, and serotonin (5-hydroxytryptamine), which normally regulate the limbic system. Deficiencies in these neurotransmitters lead to excessive excitation of the sympathetic nervous system, resulting in the physical manifestations of anxiety.

Insomnia, the inability to fall or maintain sleep, involves dysfunction in the communication between the pineal gland (melatonin production), hypothalamus (suprachiasmatic nucleus and ventrolateral preoptic nucleus - VLPO), and reticular formation. Low melatonin and GABA levels, along with high orexin and histamine levels, inhibit the VLPO (which promotes sleep) and stimulate the reticular formation (which promotes arousal), leading to insomnia.

Anxiolytic drugs work by increasing serotonin or GABA activity. SSRIs (e.g., escitalopram, sertraline, paroxetine) and SNRIs (e.g., venlafaxine, duloxetine) increase serotonin by inhibiting reuptake. Buspirone directly stimulates serotonin receptors. Benzodiazepines and barbiturates act as GABA agonists, binding to the GABA-A receptor (specifically the alpha-2 subunit for anxiolysis) to increase chloride influx, causing hyperpolarization and inhibiting limbic system neurons. Barbiturates increase the duration of chloride channel opening, while benzodiazepines increase the frequency.

Hypnotic drugs aim to induce and maintain sleep. Melatonin agonists (e.g., ramelteon) activate melatonin receptors to inhibit the suprachiasmatic nucleus. GABA agonists (benzodiazepines like temazepam and flurazepam, and Z-drugs like zolpidem, zaleplon, and eszopiclone) bind to the alpha-1 subunit of the GABA-A receptor to suppress the reticular formation, promoting sleep. Orexin antagonists (e.g., suvorexant) block orexin's wakefulness-promoting effects. Antihistamines (e.g., diphenhydramine, doxepin, mirtazapine, trazodone) block histamine, preventing its wakefulness-promoting action.

For acute anxiety, benzodiazepines are first-line due to rapid action, but have high abuse potential. For chronic anxiety, SSRIs or SNRIs are preferred, with PRN benzodiazepines or buspirone for breakthrough anxiety. For insomnia, treatment depends on the cause: benzodiazepines for stress-related insomnia (high abuse potential); Z-drugs (e.g., zaleplon for shorter duration) for mild to moderate insomnia; melatonin agonists (ramelteon) for sleep induction; and antidepressants with antihistamine properties (doxepin, mirtazapine, trazodone) for depression-related insomnia, offering less abuse potential.

Benzodiazepines and barbiturates cause CNS depression; barbiturates have no ceiling effect and higher abuse potential. All three (barbiturates, benzodiazepines, Z-drugs) can lead to dependence, tolerance, and rebound effects upon discontinuation. Barbiturates are potent cytochrome P450 inducers, causing significant drug interactions. Benzodiazepine overdose causes CNS depression, hypotension, bradycardia, and respiratory depression, treated with flumazenil. Withdrawal from benzodiazepines can cause rebound anxiety, seizures, and sympathetic hyperactivity, requiring slow tapering of the drug.