SN1 SHORT NOTE 5M ★ High-yield

Classify sedative-hypnotics. Describe the mechanism, uses and adverse effects of benzodiazepines.

Pharmacology · 2nd Professional — Para-Clinical

Classification of Sedative-hypnotics

Group	Drugs	Notes
Benzodiazepines — short-acting	Midazolam, triazolam, oxazepam	Rapid onset and offset; less hangover; more rebound insomnia and withdrawal
Benzodiazepines — intermediate	Lorazepam, alprazolam, temazepam, nitrazepam	Lorazepam is the drug of choice in status epilepticus, and is not metabolised to active compounds
Benzodiazepines — long-acting	Diazepam, chlordiazepoxide, clonazepam	Active metabolites accumulate; hangover and falls in the elderly; useful in alcohol withdrawal
Z-drugs	Zolpidem, zopiclone, zaleplon	Bind the same site but selectively; hypnotic without much anxiolytic or anticonvulsant action
Barbiturates	Phenobarbitone, thiopentone	Largely obsolete as sedatives — narrow margin, enzyme induction, severe dependence
Others	Melatonin and ramelteon; buspirone (5-HT1A partial agonist, anxiolytic without sedation or dependence)	—

Mechanism

GABAA is a ligand-gated chloride channel → Benzodiazepines bind an allosteric site between the alpha and gamma subunits → They increase the frequency of channel opening in response to GABA → Barbiturates instead increase the duration of opening, and at high dose open the channel directly, without GABA → Increased chloride entry → hyperpolarisation → reduced neuronal excitability

CLINICAL PEARL

Frequency against duration explains why benzodiazepines are so much safer than barbiturates. A benzodiazepine only enhances what GABA is already doing, so its effect has a ceiling — there is a limit to how much it can depress the CNS alone. A barbiturate can open the channel without GABA at all, so there is no ceiling, and respiratory arrest follows a large enough dose. That single difference transformed the safety of sedative prescribing.

Actions and Uses

Action	Use
Anxiolytic	Anxiety disorders and panic — short-term only, 2 to 4 weeks
Hypnotic	Insomnia — short-term; they reduce REM and slow-wave sleep, so the sleep is not fully physiological
Anticonvulsant	Status epilepticus (lorazepam, diazepam); febrile convulsions; clonazepam in myoclonic epilepsy
Muscle relaxant	Spasticity, tetanus, muscle spasm
Amnesia	Midazolam for endoscopy and minor procedures — anterograde amnesia is a genuine advantage
Alcohol withdrawal	Chlordiazepoxide or diazepam — prevents seizures and delirium tremens
Preanaesthetic medication	Anxiolysis and amnesia

Adverse Effects and Dependence

Sedation, drowsiness, impaired psychomotor performance and memory; additive with alcohol and opioids — the combination is a common cause of fatal respiratory depression
Falls and confusion in the elderly, in whom these drugs are a major preventable cause of hip fracture
Tolerance and dependence develop within weeks; withdrawal causes rebound anxiety and insomnia, tremor, sweating, perceptual disturbance and, with abrupt cessation, seizures
Paradoxical excitement and disinhibition, particularly in children and the elderly
Respiratory depression in overdose is mild alone but severe in combination, and marked in chronic obstructive pulmonary disease and sleep apnoea
Flumazenil is the specific antagonist, but is used cautiously — it precipitates seizures in dependent patients and in mixed overdose with a tricyclic

Applied Aspects

Prescribe for the shortest possible period, with a clear plan and an agreed stopping date; a repeat prescription that continues by default is how most long-term dependence begins
Taper slowly when withdrawing after prolonged use — over weeks to months, often converting to a long-acting agent such as diazepam first
Avoid in the elderly, in respiratory failure and in sleep apnoea, and never combine with an opioid without good reason
Treat the cause of insomnia — depression, pain, alcohol, poor sleep hygiene, caffeine; sleep hygiene advice and cognitive behavioural therapy are more effective than any hypnotic in the long term
Alprazolam is widely misused in India and is a common agent in deliberate self-poisoning and in criminal stupefaction; it is now a controlled substance

All questions in Central Nervous System Drugs

Every Pharmacology chapter →