Anxiolytics & Sedative Hyponotics Flashcards
Mention drugs with sedative-hypnotic side effects
Antidepressants
Antipsychotics
Antihistamines
BBs
Classify GABA receptors with actions
GABA-A: mediate postsynaptic neuronal inhibition
GABA-B: metabotropic (Gi-protein linked), presynaptic neuronal inhibition by inhibiting Ca++ influx & postsynaptic by K+ outflux hyperpolarization.
GABA binding site is at……..
interface between alpha & beta sub
BZD binding site is on…..
Gamma subunit or an area on alpha subunit regulated by gamma
Alpha1 subunit mediates…….while alpha2 mediates……
Sedation/hypnosis
Anxiolytic & muscle relaxant actions
Barbiturates increase…….of opening of Cl- channels while BZD increase THE…..
Duration
Frequency
Describe mechanism of action of zolpidem
Binds to BZD1 receptor subtype with alpha1 subunit related to sedation & hypnosis, facilitation of GABA inhibitory effect
GR: Barbiturates are largely replaced by BZD
- Narrow therapeutic index (dose-dependent action leading eventually to coma & death)
- No specific antidote
- More drug dependence
- Enzyme induction occurs with barbiturates but not BZD
- Acute porphyria
GR: Barbiturates have more powerful CNS depressant action
They have GABA-mimetic action and can block AMPA-R of gluatamte in high conc or even directly block Na channel
Mention the untrashort acting barbiturate & its dosage form
Thiopental
IV anesthetic
Classify BZDs according to duration of action
Long, diazepam, clonazepam
Intermediate, alprazolam, lorazepam
Ultrashort acting, midazolam
The BZD with no active metabolites & can be given IM is…..
Lorazepam
Describe BZDs metabolism
Oxidation by CYP3A4 then glucoronidation or some are conjugated directly by gluco.
GR: The clinical duration of long-acting BZD does not correlate with their actual half life times
Because they form active metabolites with long hakf lifes also due to receptor dissocaition in CNS & subsequent redistribution to fatty tissues & other areas
Enumerate effect of BZD on sleep patterns
- Dec sleep latency
- Inc Stage 2 sleep
- Dec REM sleep& so dec memory consolidation
4.dec stage 3& 4 NREM
Mention drugs metabolised directly by conjugation
Lorazepam
Oxazepam
Temazepam
List pharmacological actions of BZDs
Anxiolytic/euphoric
Sedative/hypnotic
Anesthetic
Anticonvulsant
Skeletal muscle relaxant
Alcohol withdrawal (diazepam, long acting)
Mention uses of BZDs as:
1. Anxiolytics
2. Sedative
- Anxiety & Panic disorders (Potentiate GABA in limbic system)
- Insomia, nightmares & night terrors (potentiate GABA in brainstem reticular formation)
Mention uses of BZDs as:
1. Anesthetic
2. Anticonvulsant
3. Skeletal muscle relaxant
- Conscious sedation, pre-anesthesia, balanced anesthesia (midazolam)
- Epilepsy & status epilepticus (s.e.:diazepam)
- Muscle spasticity (in inflammation, trauma, cerebral palsy, MS)
Mention adverse effects of BDZs
- Ataxia
- Anterograde amnesia
- Abuse
- Additive CNS depression
- Abnormal response (paradoxical excitement)
- Dowsiness, confusion, dec cognitive function, hangover
- Withdrawal of hypnotics, rebound insomnia & inc in REM sleep with nightmares
Describe symptoms of BZD toxicity
Prolonged sleep
Respiratory & cardiovascular depression (rare except if given IV rapidly or with other CNS depressants
Mention therapeutic uses of Flumazenil
Antidote to BZDs & zolpidem
Termination of their effect in anesthesia
Mention adverse effects of flumazenil
Agitation
Withdrawal syndrome or convulsions in BZD dependent patients
Mechanism of action of Zolpidem
Non-BZDs acting on BDZ1 receptor subtype involved in hypnosis
Enumerate advantages of Zolpidem over BZDs
- Rapid onset
- Less hangover
- Less cognitive impairment
- Less tolerance & dependence with less rebound insomnia
- Less suppression of REM sleep
…..is similar to zolpidem but with fewer effects on cognition & psychomotor function & rapid elimination
Zaleplon
Mention adverse effects of eszopiclone
Anxiety, dry mouth, headache, peipheral edema, somnolence, unpleasant taste
MT agonist is……, acts as…..
Mention its adverse effects
Ramelteon
Hypnotic
Dizziness, somnolence, fatigue
Mention use of buspirone, its advantages & disadvatages
U, selective anxiolytic, chronic anxietry, generalized anxiety disorder
A, No amnesia or dec cognitive function or additive CNS depression with alcohol or other sedatives
No ataxia nor abuse
D, delayed onset, does not treat insomnia
Agents uses to decrease sleep latency are…..while agents used for early morning awakening are……
Midazolam, lorazepam
Diazepam
Chronic insomnia is usually treated with……
Antidepressant
GR: BZD is added ti initial depression therapy
To calm the patient until antidepressant becomes effective
…….is preferred in liver cirrhosis
Lorazepam
GR: Dose of BZD should be reduced in elderly
To avoid accumulation (red liver metabolis) & prevent falls due to confusion/ataxia
