Anxiety and Sleep Flashcards
Sedative
decreases motor activity, coordination and mental acuity
Hypnotic
increases tendency to sleep from which pt easily awakened
Anesthetic
induces sleep from which pt is not easily awakened
Most anxiolytic/hypnotics are CNS ____
depressants that enhance inhibitory neurotransmission
Barbiturates
Bind to the GABAa receptor on the barbiturate binding site
-Inc chloride ion channel flux by increasing channel open time (hyperpolarize cells- decrease neuronal activity)
Complete depressants
Produce anesthesia, coma and death with increasing dose
-Include barbiturates, ethanol
Incomplete depressants
Typically do not produce anesthesia and will not induce coma or death alone
-non benzodiazepine BZ receptor agonist, benzos
GABAa receptor
GABA is primary inhibitor neurotransmitter
Pentameric ion channel coupled receptor
Effects of Barbiturates on organ systems
- CNS- complete CNS depressants with paradoxical excitement and euphoria
- Resp and CV- at anesthetic doses decreases respiration and bp
- Liver- induces expression of microsomal enzymes resulting in inc activity–> pharmacokinetic tolerance and dec plasma levels of other drugs
- Inc porphyrin synthesis which can aggravate porphyria
Toxicity of Barbiturates
Overdose or interaction with other CNS depressants- dec in resp and bp, loss of consciousness
- no specific antagonist
Chronic will lead to tolerance (kinetic and dynamic)
- Addiction, withdrawal (anxiety, tremor, seizures, hyperthermia, cv collapse– can be fatal; cell is working normally with dose of drug, w/o drug will lead to opposite of what the drug was doing)
- tx: measured reduction over time (tx seizures and anxiety with benzos)
Barbiturates and their uses
Phenobarbital (long acting) Pentobarbital (med acting) Secobarbital (med acting) Methohexital (iv) Amobarbital (iv) Thiopental (iv)
-sedative, hypnotics, anticonvulsants, drug induced coma, preanesthetic, anesthetics, WADA test (map language and memory fxns), narcoanalysis (truth serum), euthanasia/lethal injection (vet practice, capital punishment)
Pharmacokinetics of barbs
- readily diffuses across all membranes
- distributes throughout body depending on lipophilicity
- crosses placenta (fetal addition)
- Highly protein bound- drug interactions
- metabolized in liver
- excreted in urine
Benzodiazepines MOA
Bind to benzodiazepne binding sites (BZ) on GABAa receptor (allosteric activator)
- inc affinity of GABAa receptors for GABA, which increases likelihood of channel opening
- Act on smaller subset of GABAa receptors than barbs due to diff expression of subunits that make up pentamer (BZ1, BZ2, BZ3)
- various receptor subunits can lead to diff binding sites and as well as phamacokinetic differences
Effect of benzos on organ systems
-of Diazepam
CNS- incomplete depressant, dec anxiety, skeletal muscle relaxant, anticonvulsant, hypnotic
-paradoxical excitement and euphoria
-Tolerance- sedative, hypnotic, anticonvulsant actions
-No sig effects on respiratory, CV, and GI systems
Side effects and toxicities of benzos
(diazepam)
- Sedation and ataxia
- Amnesia (esp midazolam)
- Nightmares, irritability, anxiety, seizures
- Overdose tx with flumazenil (reverses sedation)
- Withdrawal with shorter acting drugs (rebound anxiety with alprazolam) –> anxiety, irritability, insomnia, nausea, vomiting, tremor, sweating, anorexia, confusion, psychosis, seizures
Short acting benzos
2-4 hrs
Midazolam- rapidly inactivated, iv anesthesia
Triazolam- hypnotic
Mod acting benzos
10-14 hrs
Alprazolam- anxiolytic/ hypnotic, panic attacks; rapid oral absorption/onset
Chlordiazepoxide- anxiolytic, pre-anesthetic
Lorazepam- anxiolytic/hypnotic, pre-anesthetic
Long acting benzos
24 hrs
Clonazepam- anticonvulsant
Very long acting (active metabolites) benzos
Diazepam- anxiolytic, anticonvulsant, muscle relaxant, antispastic, pre-anesthetic (43 hr 1/2 life)
Flurazepam (1/2 life 72 hrs)
Other benzos
Flunitrazepam- fast acting, “Date rape”, amnestic, no therapeutics
Flumazenil
reverses overdose and anesthesia from benzos
-short 1/2 life
Pharmacokinetics of benzos
rapidly absorbed from GI
most administered orally but some from IV or IM (diazepam, lorazepam, midazolam)
highly protein bound, however, few drug interactions
crosses placenta
numerous active metabolites (esp long acting)
metabolized in liver
excreted in urine
Non benzo BZ receptor agonists
BZ1 agonists- zolpidem, zaleplon
Non selective agonists- eszopiclone
Hypnotic, short 1/2 life, minimal muscle relaxant or anticonvulsant activity, less amnestic than benzos, claimed to produce less tolerance to hypnotic effects than benzos
SE of non benzo BZ receptor agonists
-Abnormal thinking/behavior (sleepwalking, raiding refrigerator, amnesia, hallucinations)
Buspirone
- Nondepressant anxiolytics
- Partial agonist at 5-HT1a site
- Slow onset of action 1-2 weeks
- Dysphoric at high doses
SSRIs and other antidepressants
non-depressant anxiolytic
inc synaptic availability of 5-HT
-used for generalized anxiety and as prophylaxis for panic disorder
Hydroxyzine
non-depressant anxiolytic
- H1 blocker
- Used pre and post op
- antipruritic and anti-emetic
Melatonin agonist
Ramelteon
- nondepressant drug for insomnia
- indicated for insomnia with prolongd sleep onset
- MT1 and MT2 melatonin receptor agonist
Orexin antagonist
Suvorexant
-indicated for diff with sleep onset and/or sleep maintenance
Antihistamines
Diphenhydramine
H1 blocker
OTC sedative
Trazodone
-non depressant drug for insomnia
Blocks 5-HT reuptake, H1 and a1 receptors
antidepressant, but also sedating so it’s used as a hypnotic
