3. Sedation II Flashcards
Site of action of benzos
-GABA A receptor
Role of the GABA A receptor
- Inhibitory receptor
- Allows for influx of Cl
Clinical effects of benzos/uses
- Anxiety reduction
- Sedation (pre-appointment)
- Hypnosis (sleep production)
- Anterograde amnesia
What is anterograde amnesia
Loss of ability to create new memories after the event that caused amnesia (in this case taking the benzo)
Effects of benzos on the respiratory system
*respiratory depression (at high doses)
Benzos have an additive effect with what other drugs
- Other CNS depressants (alcohol, narcotics, other sedatives/hypnotics)
- Hypotensive agents (Ca channel blockers)
Location of GABA A receptors
cerebral cortex and limbic system
CYP3A inducers are
- Rifampin
- Phenytoin
- Carbamazepine
Absolute contraindications for benzos are
- Allergy
- Narrow angle glucoma
- Pregnant patients (teratogenic agent –> congenital craniofacial anomalies)
Percautions in benzo use
- Extremes in age (really young and old- diphenhydramien as alternative)
- Suicide potential
- Abuse potential
- Respiratory impairment
Two commonly used benzos are
midazolam and diazepam
What is the advantages of midazolam over diazepam
midazolam= no active metabolites
-Shorter half life (fast on and fast off)
Benzo reversal agent is
flumazenil
MOA of flumazenil
Competitive antagonist against benzo binding site on GABA A
Chloral hydrate is reduced to what intermediate by what enzyme
trichloroethanol by alcohol dehydrogenase in the liver
What happens the the metabolite trichloroethanol
conjugated with glucuronic acid and excreted renally
Drug interactions with chloral hydrate
- CNS depressants (potentiation)
- Coumarin/inanedione anticoagulants (displace anticoagulant from protein binding site)
Absolute contraindication for chloral hydrate
- Allergy
- Porphyria
- Severe hepatic impairment
- Severe renal function
- Severe cardiac disease
Relative contraindications for chloral hydrate
- Pregnant/nursing
- Esophagitis
- Gastritis
- Peptic ulcers
- Drug/EtOH dependence
MOA of antihistamines
reversible competitive inhibition at the H1 receptor with histamine
Benefits of anti-histamines
- Anxiety reduction
- Sedation
- Antiemetic
- Anti-cholinergic
Drug interactions with Diphenhydramine
CNS depressants (like alcohol)
Which has a faster onset of action (Diphenhydramine or hydroxazine)
Hydroxizine
Drug interactions for hydroxyzine
Same as diphenhydramine (CNS depressants)
Contraindications for hydroxyzine
- Allergy
- Pregnant/nursing moms (fetal abnormalities in rats0 not known if secreted in the breast milk)
What class of drug is Zolpidem
Imidazopyridine
MOA of Zolpidem
- Binds the omega site on GABA A
- Unrelated to benzo MOA
- Enhances affinity of GABA for Chloride conductance and hyperpolarization
Advantage of Zolpidem
less amnestic effect than benzos (mental impairment)
-Rapid onset and short duration
Excessive amounts of benzos have what effects on the cardiovascular and pulmonary system
decreased CV and lung function (depression)
Administration of flumazenil is (IV/IM)
IV only
Major advantage of antihistimines for sedation
anti-emetic (block muscarinic cholinergic receptors in the chemoreceptor trigger zone (CTZ)
What sedative causes gastric irritation
chloral hydrate
What sedatives have an anticholinergic effect
anti-histamines
Generic name for Zolpiden is
ambien
